Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.
Cancer is a complex genetic disease that comprises specific hallmarks. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, apart from reprogramming of energy metabolism and evading immune destruction [
In these recent years, a large number of studies have documented the efficacy of essential oils and their chemical constituents as source of new bioactive natural products [
Cancer is a major cause of death worldwide, ranked behind only cardiovascular disease. Considering that monoterpenes are common in many plant species and are used in cosmetic and pharmaceutical preparations, as well as the food industry, it is important to review the pharmacological potential of monoterpenes with anticancer activity.
The present study was carried out based on the literature review of monoterpenes from essential oils with antitumor activity. Chemical structures and names of bioactive compounds are provided. The monoterpenes presented in this review were selected with reference to effects shown in specific experimental models for evaluation of antitumor activity and/or by complementary studies aimed to elucidate mechanisms of action Table
Essential oils monoterpenes with antitumor activity.
Compound | Antitumor activity and/or mechanism | Animal/cell line tested | IC50, |
Reference |
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Active (cell cycle arrest; induction of apoptosis) | |
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[ |
Human colon cancer cell lines HCT-116 (p53−/−) |
10–30% |
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Active (cell cycle arrest; induction of apoptosis) | |
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[ |
Human colon cancer cell lines HCT-116 (p53−/−) |
10–30% |
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HeLa (epithelioid carcinomic cell line) | ND | |||
Active (ND) | MOLT-4 (human lymphoblastic leukemia T-cell line) | ND | [ | |
K-562 (human chronic myelogenous leukemia cell line) | ND | |||
CTVR-1 (early B-cell line from the bone marrow cells of a patient with acute myeloid leukemia) |
ND |
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Active (inhibition of the NF- |
Small cell lung carcinoma |
0.26 mM |
[ |
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Active (ND) | Mouse P388 leukemia cell | 34–54 |
[ |
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Active (inhibition gene expression of topoisomerases I, II alpha, and II beta and promoting the gene expression of NF- |
SNU-5 (human gastric carcinoma cell line) |
1.62 mg/mL |
[ |
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Active (TRPM8 channel activation; cell cycle arrest) | DU145 (human prostate carcinoma cell line) | 53.41–90.66% |
[ | |
Active (mitochondrial membrane depolarization via the TRPM8 channel) | T24 (Human bladder cancer cell line) | ND | [ | |
Active (agonist of TRPM8) |
Oral squamous carcinoma cell lines (HSC3 and HSC4) |
ND |
[ |
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Active (ND) | |
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[ |
Ehrlich's ascites carcinoma |
75%b |
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Active (ND) | |
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[ |
Ehrlich's ascites carcinoma |
87%b |
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Active (ND) | |
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[ |
Ehrlich's ascites carcinoma |
91%b | |||
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Active (ND) | |
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[ |
Caco-2 (colon malignant cell line) | 2250 | |||
Active (potentiates selenocystine-induced apoptosis and activation of ROS-mediated DNA damage) | HepG2 (hepatocellular carcinomic human cell line) |
ND |
[ | |
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Active (ND) | HL60 (acute promyelocytic cancer cell line) | ND | [ | |
MDA-MB-231 (Human metastatic breast cancer cell line) | ND | |||
Active (ND) | HL-60 (acute promyelocytic cancer cell line) | 6.3 |
[ | |
HCT-8 (ileocecal colorectal adenocarcinoma) |
18.4 |
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Active (ND) | Sarcoma 180 ( |
10 or 20 mg/kg | [ |
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Active (ND) | Mouse leukemia P388 cell line | ND | [ |
P815 (mastocytoma cell line) | <0.004% v/v | [ | ||
P815 (mastocytoma cell line) | 1.2% v/v · 10−2 | [ | ||
K-562 (human chronic myelogenous leukemia) | 1.2% v/v · 10−2 | [ | ||
Active (cell cycle arrest; induction of apoptosis) | CEM (acute T lymphoblastic leukemia) | 1.2% v/v · 10−2 | [ | |
MCF-7 (human breast adenocarcinoma) | 2.5% v/v · 10−2 | [ | ||
MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) | 0.85% v/v · 10−2 | [ | ||
P815 (mastocytoma cell line) | 0.067 |
[ | ||
K-562 (human chronic myelogenous leukemia) | 0.067 |
[ | ||
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CEM (acute T lymphoblastic leukemia) | 0.042 |
[ | |
Active (cell cycle arrest; induction of apoptosis) | MCF-7 (human breast adenocarcinoma) | 0.125 |
[ | |
MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) | 0.067 |
[ | ||
Active (induction of apoptosis) | Hep2 (larynx epidermoid carcinoma) | 0.22–0.32 mM* | [ | |
Active (induction of apoptosis) | HepG2 (hepatocellular carcinomic human cell line) | 0.4 mmol/L | [ | |
Active (induction of apoptosis) | MDA-MB 231 (human metastatic breast cancer cell line) | 100 |
[ | |
HepG2 (hepatocellular carcinomic human cell line) | ND | [ | ||
Active (antioxidant activity) | Caco-2 (colon malignant cell line) | ND | [ | |
K562 (erythromyeloblastoid leukemia cell line) | 150–200 |
[ | ||
Active (ND) | HepG2 (hepatocellular carcinomic human cell line) | 350 |
[ | |
Caco-2 (colon malignant cell line) | 600 | |||
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Myoblast cells | 60 |
[ | ||
Active (prevention of hepatocellular carcinogenesis) | DEN-induced hepatocellular carcinogenesis | 15 mg/kg | [ | |
Active (ND) |
HepG2 (hepatocellular carcinomic human cell line) |
53.09 |
[ |
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Active (ND) | Mouse leukemia P388 cell line | 1.1 |
[ |
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HepG2 (hepatocellular carcinomic human) | >25 |
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Active (cell cycle arrest; induction of apoptosis) | K562 (erythromyeloblastoid leukemia cell line) | ND | [ | |
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B16-F10 (melanoma) |
9.28 |
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Active (ND) | Hep-2 (larynx epidermoid carcinoma) | 0.71–0.78 mM* | [ |
Active (ND) | HepG2 (hepatocellular carcinomic human cell line) | 400 |
[ | |
Caco-2 (colon malignant cell line) | 700 | |||
Active (ND) | Mouse leukemia P388 cell line | ND | [ | |
Active (ND) | Mouse leukemia P388 cell line | 0.80 |
[ | |
P815 (mastocytoma cell line) | 0.015% v/v | [ | ||
P815 (mastocytoma cell line) | 3.1% v/v · 10−2 | [ | ||
K-562 (human chronic myelogenous leukemia) | >22% v/v · 10−2 | [ | ||
Active (cell cycle arrest and apoptosis) | CEM (acute T lymphoblastic leukemia) | 6.9% v/v · 10−2 | [ | |
MCF-7 (human breast adenocarcinoma) | >22% v/v · 10−2 | [ | ||
MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) | >22% v/v · 10−2 | [ | ||
P815 (mastocytoma cell line) | 0.15 |
[ | ||
K-562 (human chronic myelogenous leukemia) | 0.44 |
[ | ||
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CEM (acute T lymphoblastic leukemia) | 0.31 |
[ | |
Active (cell cycle arrest and apoptosis) | MCF-7 (human breast adenocarcinoma) | 0.48 |
[ | |
MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) | ND | [ | ||
HepG2 (hepatocellular carcinomic human cell line) | ND | [ | ||
Active (antioxidant activity) | Caco-2 (colon malignant cell line) | ND | [ | |
K562 (erythromyeloblastoid leukemia cell line) | 400–500 |
[ | ||
Active (cell cycle arrest; induction of apoptosis) | HL-60 (acute promyelocytic cancer cell line) | ND | [ | |
Active (ND) | HepG2 (hepatocellular carcinomic human cell line) | 60.01 |
[ | |
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Active (ND) | Fibrosarcoma (FsaR) cell lines ( |
92%c | [ | |
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Fibrosarcoma (FsaR) cell lines ( |
20 mg/kg |
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A549 (lung carcinoma cell line) | 72.0–146 |
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Active (induction of apoptosis) | HEp-2 (larynx epidermoid carcinoma cell line) | 22.9–34.6 |
[ | |
HT-29 (colon adenocarcinoma cell line) | 51.0–53.3 | |||
MIA PaCa-2 (pancreas carcinoma cell line) | 60.0–67.9 |
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SF-539 (central nervous system cancer cell line) | ND | |||
PC-3 (prostate cancer cell line) | ND | |||
Active (ND) | M-14 (melanoma) | ND | [ | |
OVCAR-5 (ovarian cancer cell line) | ND | |||
MCF-7 (breast adenocarcinoma cell line) | ND | |||
Active (ND) | A-549 (lung carcinoma cell line) | 13.0 |
[ | |
DLD-1 (colorectal adenocarcinoma cell line) | 5.9 | |||
SCC VII (squamous cell carcinoma) | 86%c | |||
Active (ND) | Fibrosarcoma (FsaR) cell lines ( |
92%c | [ | |
Fibrosarcoma (FsaR) cell lines ( |
20 mg/kg | |||
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Active (proteasome inhibition and induction of apoptosis) | U87 MG (malignant glioma cells) |
61.46–77.73 |
[ |
Active (induction of apoptosis) | NCI-H460 (nonsmall cell lung cancer cell line) |
ND |
[ | |
Active (downregulation of NF- |
Mouse xenograft model using NCI-H460 (human large cell lung cancer) | 20 mg/kg | [ | |
Active (suppression of the NF- |
KBM-5 (human myeloid cell line) |
ND |
[ | |
Active (suppression of STAT3 activation and induction of apoptosis) | Multiple myeloma | ND | [ | |
Active (inactivation of the stress response pathway sensor CHEK1 and induction of apoptosis) | Human colon cancer cell lines |
ND | [ | |
Active (ND) | Ehrlich ascites carcinoma bearing mice |
50 mg/L |
[ | |
Active (downregulation of NF- |
Orthotopic model of pancreatic cancer ( |
ND |
[ | |
Active (antioxidant activity) | Fibrosarcoma induced by 20-methylcholanthrene (MC) in male Swiss albino mice ( |
ND |
[ | |
Active (antioxidant activity) | Osteoblasts cells (MG 63) in tissue culture | 32–64% |
[ | |
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Active (inhibition of NF- |
Osteosarcoma ( |
ND |
[ | |
Active (induction of apoptosis via p53-dependent pathway) |
HeLa (epithelioid carcinomic cell line) |
2.80–5.93 mg/mL* |
[ |
|
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Active (involvement of reactive oxygen species and activation of ERK and JNK signaling) | Caco-2 (human colon cancer cell) | 12.5–15.0 |
[ |
HCT-116 (human colon cancer cell) | 14–30 | |||
LoVo (human colon cancer cell) | 28–38 | |||
DLD-1 (human colon cancer cell) | 23–42 | |||
HT-29 (human colon cancer cell) | 110 | |||
Active (binding to bovine serum albumin) | DLD-1 (human colon cancer cell) | ND |
[ | |
HCT-116 (human colon cancer cell) | ND | |||
Active (ND) | A549 (human nonsmall cell lung cancer (NSCLC) cell line) | ND | [ | |
Active (antioxidant activity) | ES-2 (ovarian cancer cell line) | ND | [ | |
Active (prooxidant cytotoxic mechanism) | Prostate cancer cell lines | ND | [ | |
Active (ND) | 66 cl-4-GFP (resistant mouse mammary gland cell line) |
10 mg/kg | [ | |
Active (disruption in cell-cycle checkpoints) | LNCaP (prostate cancer cell line) |
ND |
[ | |
Active (induction of apoptosis) | p53-null myeloblastic leukemia HL 60 cells | 23 |
[ | |
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Active (increase of ROS generation and decreased GSH levels) | Androgen receptor (AR) independent (C4-2B) | 100 |
[ |
AR naive (PC-3) prostate cancer cells | 86 |
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Active (cell cycle arrest; induction of apoptosis) | COS31 (canine osteosarcoma) | ND | [ | |
Active (cell cycle arrest; induction of apoptosis) | HepG2 (hepatocellular carcinomic human cell line) | 350 |
[ | |
Active (cell cycle arrest, increase in the expression of the protein p53 and decrease in cyclin B1 protein) | Primary mouse keratinocytes, SP-1 (papilloma) |
30 |
[ | |
Active (inhibition of telomerase) | Human glioblastoma cells | ND | [ | |
Active (inhibition of PDE1A expression) | Jurkat cell (acute lymphoblastic leukemia cell line) | ND | [ | |
Active (downregulated MUC4 expression and induction of apoptosis) | The MUC4-expressing pancreatic cancer cells FG/COLO357 |
73 |
[ | |
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Active (upregulation of PTEN expression and induction of apoptosis) | Doxorubicin-resistant human breast cancer MCF-7/DOX cell | 35–70%a | [ |
Active (ND) | Parental and multidrug resistant (MDR) human tumor cell lines | 78 |
[ | |
Active (thymoquinone-loaded nanoparticles activity) | MDA-MB-231 (human metastatic breast cancer cell line) | ND | [ | |
Active (comparison of thymoquinone versus thymoquinone-loaded nanoparticles activities) | HCT-116 (colon cancer cell line) | 15% versus 85%b | [ | |
MCF-7 (breast cancer cell line) | 30% versus 88%b | |||
PC-3 (prostate cancer cell line) | 30% versus 85%b | |||
U-266 (multiple myeloma cell line) | 55% versus 70%b | |||
HCT116 (colon cancer cell line) | 24%c | |||
Activity of derivatives of thymoquinone | HCT116p53−/− colon cancer | 72%c | [ | |
HepG2 (hepatocellular carcinomic human cell line) | 75%c | |||
HL-60 (acute promyelocytic leukemia cells) | 0.13–>100 |
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Activity of analogs of thymoquinone | 518A2 (melanoma cell line) | 3.9–>100 |
[ | |
multidrug-resistant KB-V1/Vbl cervix | 7.0–79.9 | |||
MCF-7/Topo (breast carcinoma) | 2.8–>100 |
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Active (ND) | Mouse Ehrlich ascites carcinoma tumor | ND | [ |
Active (inhibition of Akt phosphorylation; induction of apoptosis; inhibition of HDAC2 proteins) | LNM35 (human lung cancer cell) | 50–78 |
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HepG2 (human hepatoma cell) | 34 |
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HT29 (human colorectal cancer cell) | 50–78 |
[ | ||
MDA-MB-435 (human mammary adenocarcinoma cell) | 50–78 | |||
MDA-MB-231 (human mammary adenocarcinoma cell) | 50–78 |
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MCF-7 (human mammary adenocarcinoma cell) | 50–78 |
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Active (ND) |
|
1, 2 or 4 mg/kg | [ | |
Active (cell cycle arrest; induction of apoptosis via Akt modulation) | MDA-MB-468 (human mammary adenocarcinoma) | 12.30 |
[ | |
T-47D (human mammary ductal carcinoma) | 18.06 | |||
Active (induction of apoptosis) | HL-60 (human promyelocytic leukemia cell) | 27.8 |
[ | |
518A2 (melanoma cell line) | 28.3 | |||
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HT-29 (colon carcinoma cell) | 46.8 |
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Active (induction of apoptosis) | KB-V1 (cervix carcinoma cell) | 25.8 |
[ | |
MCF-7 (human mammary adenocarcinoma cell) | 20.1 | |||
Multidrug-resistant variants | 18.7–57.2 |
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MCF-7 (breast cancer cell line) | 32–48 |
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Active (modulation of the PPAR- |
MDA-MB-231 (breast cancer cell line) | 11–24 |
[ | |
BT-474 (breast cancer cell line) | 18–38 |
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Active (condition T cells |
OT-1 (transgenic CD8+) T cells | ND | [ | |
Active (induction of apoptosis) | Mouse model of familial adenomatous polyposis | 375 mg/kg | [ | |
Active (comparison of thymoquinone and thymoquinone in liposomes effects) | MCF-7 (breast cancer cell line) |
40 |
[ | |
A431 (human epidermoid carcinoma) | 10 |
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Active (cell cycle arrest and induction of apoptosis) | Hep-2 (larynx epidermoid carcinoma) | 10 |
[ | |
Sarcoma 180 |
10 mg/kg | |||
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Active (antimicrotubule drug) | |
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[ |
Jurkat cells (acute lymphoblastic leukemia cell line) |
ND |
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Active | Mouse P388 leukemia cell | ND | [ |
HeLa (human cervical carcinoma) | >200 |
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Active (ND) | A-549 (human lung carcinoma) | >200 |
[ | |
HT-29 (human colon adenocarcinoma) cell lines | >200 |
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Crown gall tumors | 50%b | |||
Active (ND) | MCF-7 (breast carcinoma) |
< |
[ | |
HT-29 (colon adenocarcinoma) | < |
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A-549 (lung carcinoma) | < |
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Active (cell cycle arrest and induction of apoptosis) | HepG2 (hepatocellular carcinomic human cell line) | 9.23 |
[ | |
B16F10 (murine melanoma) | 12.27 | |||
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Active (cell cycle arrest and induction of apoptosis) | B16F10 (murine melanoma) |
12.27 |
[ |
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Active (induction of the hepatic detoxification enzymes glutathione S-transferase GST and uridine diphosphate-glucuronosyltransferase UDPGT) | DMBA-induced rat mammary carcinogenesis | ND | [ |
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Active (antitumorigenic effects induction of apoptosis) | Pancreatic, mammary, and prostatic tumors | ND | [ |
Active (inhibition of the isoprenylation of small G proteins) | DMBA- and 5NMU-induced rat mammary carcinomas | 10% in diet | [ | |
Active (combined limonene and 4-hydroxyandrostrenedione) | NMU-induced rat mammary carcinomas | 5% limonene and 4-hydroxyandrostrenedione (12.5 mg/kg) | [ | |
Active (ND) | DMBA-induced rat mammary carcinogenesis | ND | [ | |
Active (induction of apoptosis and antiangiogenic effect) | SW480 (human colorectal adenocarcinoma) | ND | [ | |
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Active (induction of apoptosis and antiangiogenic effect) | HT-29 (colon adenocarcinoma) | ND | [ |
Active (immunomodulatory effect) | BW5147 (murine T cell lymphoma) | 35 |
[ | |
Active (ND) | B16F-10 (melanoma cells in mice) | 100 |
[ | |
Active (induction of the hepatic detoxification enzymes glutathione S-transferase GST and uridine diphosphate-glucuronosyltransferase UDPGT) | DMBA-induced rat mammary carcinogenesis | ND | [ | |
Activity of derivatives limonene (inhibition of protein prenylation) |
|
ND | [ | |
Active (inhibition of NNK metabolic activation) | NNK-induced lung tumorigenesis in mice | 183 |
[ | |
Active (ND) | AflatoxinB1-induced hepatocarcinogenesis | 5% in diet | [ | |
Active (induction of apoptosis) | K562 (erythromyeloblastoid leukemia cell line) |
ND |
[ | |
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Active (ND) | Colonic carcinogenesis in rats | 5% | [ |
Active (high affinity with HMG-CoA reductase) |
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ND | [ | |
Active (increase of GST activity) | Several tissues of female A/J mice | 20 mg/0.3 mL of the oil | [ | |
MCF-7 (human breast adenocarcinoma) | 14 |
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Active (ND) | K562 (erythromyeloblastoid leukemia cell line) | 16 |
[ | |
PC12 (rat adrenal pheochromocytoma cell line) | >100 |
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A-549 (lung carcinoma) | <10 |
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Active (ND) | MCF-7 (breast carcinoma) | <10 |
[ | |
HT-29 (colon adenocarcinoma) | <10 |
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A-549 (lung carcinoma) | ND | |||
Active (effect on gap junction intercellular communication) | W1-38 (human fibroblast lung normal cells) | ND | [ | |
CACO2 (human colorectal adenocarcinoma) | ND | |||
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Active (ND) | A-549 (lung carcinoma) | 0.098 |
[ | |
HepG2 (hepatocellular carcinomic human cell line) | 0.150 |
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Active (ND) | Molecular docking | ND | [ | |
Active (involvement of c-myc oncoprotein) |
NDEA induced hepatocarcinogenesis |
5% in diet |
[ |
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Active (cell cycle arrest; induction of apoptosis) | SCC-25 (human head and neck squamous cell carcinoma cell line) | 19%c | [ | |
BroTo (human head and neck squamous cell carcinoma cell line) | 9%c | |||
Active (cell cycle arrest; induction of apoptosis) | A549 (human lung adenocarcinoma) |
3.6 mM |
[ | |
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Active (induction of apoptosis) | 9,10-Dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis | 6 or 12 mg/kg | [ |
Active (cell cycle arrest; induction of apoptosis) | Advanced rat mammary carcinomas | 0.1 g/kg | [ | |
Active (cell cycle arrest; induction of apoptosis) | Bcr/Abl-transformed leukemia cells | ND | [ | |
Active (cell cycle arrest and induction of apoptosis) | Bcr/Abl-transformed myeloid cell lines | 300–400 |
[ | |
Active (ND) | Hamster pancreatic tumors | 1.2–2.4 g/kg | [ | |
Active (ND) | MIA PaCa2 (human pancreatic tumor cells) | 60–90%2 |
[ | |
PC-1 (hamster pancreatic adenocarcinoma) | 40 g/kg | |||
Active (induction of Bak-induced apoptosis) | B12/13 (pancreatic adenocarcinoma cell line) | 150 |
[ | |
Active (inhibition of the prenylation of growth-regulatory proteins) | Pancreatic adenocarcinoma cells | ND | [ | |
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AsPC-1 (pancreatic adenocarcinoma cell line) | 300 |
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Active (induction of apoptosis) | MIA PaCa-2 (pancreatic adenocarcinoma cell line) | 350 |
[ | |
PANC-1 (pancreatic adenocarcinoma cell line) | 350 | |||
BxPC-3 (pancreatic adenocarcinoma cell line) | 550 |
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Active (induction of apoptosis) | K562 (erythromyeloblastoid leukemia cell line) | 81.0 |
[ | |
Active (antiangiogenic activity) | BLMVECs (bovine lung microvascular endothelial cells) | ND | [ | |
Active (c-Myc-dependent apoptosis) | Bcr/Abl-transformed leukemia cells | ND | [ | |
Active (cell cycle arrest; induction of apoptosis) | A549 (human lung adenocarcinoma epithelial cell line) |
1.4 mM |
[ | |
Active (inhibition of Na+/K+-ATPase activity) | Guinea pig brain and kidney were used in the preparation of homogenates and Na/K-ATPase-enriched fractions | 1.0 mM for the brain enzyme and 1.5 mM for the kidney enzyme | [ | |
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Active (inhibition of protein isoprenylation and cell proliferation) | HT-29 (colon adenocarcinoma cell) | ND | [ |
Active (modulation of the expression of AP-1 target genes) | Breast cancer cells | ND | [ | |
Active (antitumor effect potentiated by hyperthermia) | SCK mammary carcinoma cells of A/J mice | 20–58%a | [ | |
Active (inhibition of ubiquinone synthesis and block of the conversion of lathosterol to cholesterol) | NIH3T3 (mouse fibroblast cell line) | ND | [ | |
Active (activity of metabolites of perillyl alcohol) | Inhibition of protein prenyltransferases |
1 mM | [ | |
Active (inhibition of the |
NIH3T3 (mouse fibroblast cell line) | 0.5 or 1.0 mM | [ | |
Active (ND) | AflatoxinB1-induced hepatocarcinogenesis | 2% in diet | [ | |
Active (antimetastatic activity) | C6 (glial cell line) | ND | [ | |
Active (phases I/II study) | Human malignant gliomas | 0.3% v/v | [ | |
Active (pretreated before exposure to radiation) | HTB-43 (head and neck squamous cell carcinoma cell line) | 71%b | [ | |
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BroTo (head and neck squamous cell carcinoma cell line) | 53%b | |||
Active (radio-/Chemosensitizer) | Glioma cells | ND | [ | |
Active (cell cycle arrest; induction of apoptosis) | PC12 (rat adrenal pheochromocytoma cell line) | ND | [ | |
Active (pharmacokinetics studies) | Pharmacokinetics studies in dogs | ND | [ | |
Active (phase I) | Human advanced malignancies | 800–2400 mg/m2/dose | [ | |
Active (telomerase activity) |
Prostate cancer cells |
ND |
[ | |
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Active (ND) | HepG2 (hepatocellular carcinomic human cell line); |
ND | [ |
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[ |
Active (induction of apoptosis) | KB (human papilloma cell line) | ND | [ | |
SK-OV-3 (human ovarian adenocarcinoma) | 1.10 |
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Active (ND) | HO-8910 (human epithelial ovarian cancer) | 2.90 |
[ | |
Bel-7402 (human hepatocellular carcinoma) | 3.47 |
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Active (binds to the Caspase 3) |
Molecular docking studies |
ND |
[ |
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Active (ND) | K-562 (human chronic myelogenous leukemia cell line) | ND | [ | |
PC-12 (rat adrenal gland pheochromocytoma) |
ND |
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HepG2 (hepatocellular carcinomic human cell line) | ND | ||
HeLa (epithelioid carcinomic cell line) | ND | |||
Active (ND) | MOLT-4 (human lymphoblastic leukemia T-cell line) | ND | [ | |
K-562 (human chronic myelogenous leukemia cell line) | ND | |||
CTVR-1 (early B cell line from the bone marrow cells of a patient with acute myeloid leukemia) | ND | |||
Active (induction of apoptosis) | Human melanoma M14 WT cells and their resistant variants | ND | [ | |
Active (ND) | Drug-sensitive and drug-resistant melanoma cells | ND | [ | |
Active (cell cycle arrest and induction of necrosis) | AE17 (mesothelioma murine cancer cells) |
0.01–0.02 |
[ | |
Active (ND) | A-549 (lung carcinoma); DLD-1 |
>100 |
[ | |
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Active (ND) | MCF-7 (breast carcinoma) | 92.3%c | [ | |
Active (induction of apoptosis-activating p53) | Endometrial cancer cell lines Ishikawa and ECC-1 (endometrial carcinoma cell line) | 2.3 |
[ | |
Active (induction of apoptosis) |
NB4 (acute promyelocytic leukemia cell line) |
3.995 |
[ |
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Active (ND) | HeLa (human cervical carcinoma) | 74.5 |
[ | |
Active (induction of oxidative stress) | Cultured primary rat neuron and N2a neuroblastoma (NB) cells | ND | [ | |
Active (ND) |
MCF-7 (breast carcinoma) | 0.63 |
[ | |
K-562 (human chronic myelogenous leukemia cell line) | 0.17 | |||
P-815 (mouse lymphoblast like mastocytoma cell line) | 0.16 | |||
CEM (human acute lymphoblastic leukemia) |
0.11 | |||
|
||||
|
Active (oxidative stress and reporter gene activities of antioxidant response element (ARE), activator protein 1 (AP-1), and nuclear factor NF- |
A549 (lung carcinoma) |
250 ppm |
[ |
Active (immunomodulatory effect) | BW 5147 (murine T cell lymphoma) |
1100 |
[ | |
HepG2 (hepatocellular carcinomic human cell) | 1393.3 |
|||
K562 (human chronic myelogenous leukemia cell line) | 679.1 |
|||
Active (ND) | H-460 (lung large cell carcinoma) | 501.8 |
[ | |
N-87 (gastric carcinoma) | 840.6 |
|||
SW-620 (colon adenocarcinoma) | 786.2 |
|||
Active (ND) | Dual reverse virtual screening protocol | ND | [ | |
Active (ND) | SK-OV-3 (human ovarian adenocarcinoma) |
0.052 |
[ | |
|
||||
|
Active (ND) | Bel-7402 (human hepatocellular carcinoma) | 0.32 |
[ |
Active (ND) | MCF-7 (mammary adenocarcinoma) |
64.3 |
[ | |
Active (induction of apoptosis) | U937 (histiocytic lymphoma cells) | ND | [ | |
HeLa (human cervical carcinoma) | 172.7 |
|||
Active (ND) | A-549 (human lung carcinoma) | 183.2 |
[ | |
HT-29 (human colon adenocarcinoma) | >200 |
|||
MCF-7 (human breast carcinoma cell line) | 20.6 |
|||
Active (ND) | MDA-MB-468 (human breast carcinoma cell line) | 39.2 |
[ | |
UACC-257 (human breast carcinoma cell line) | 16.3 |
|||
|
||||
|
Active (ND) | A-549 (lung carcinoma) |
85.0 |
[ |
MCF-7 (breast carcinoma) | ||||
Active (ND) | A375 (human melanoma) | ND | [ | |
HepG2 (hepatocellular carcinomic human cell line) | ||||
Active (immunomodulatory effect) | BW5147 (murine T cell lymphoma) | 114.81 |
[ | |
MCF-7 (breast carcinoma) | 176.5–242.6 mM* | |||
Active (ND) | A375 (human melanoma) | 198.5–264.7 |
[ | |
HepG2 (hepatocellular carcinomic human cell) | 147.1–198.5 |
|||
Active (ND) | MCF-7 (human breast carcinoma cells) |
ND |
[ | |
Active (ND) | Dual reverse virtual screening protocol | ND | [ | |
|
||||
|
Active (cell cycle arrest) | (Caco-2) human colon cancer cell line | 70%a | [ |
Active (blockade of the morphological and functional differentiation of the cells) | Human colonic cancer cells | 30%c | [ | |
Caco-2 (human epithelial colorectal adenocarcinoma cells) | 250 |
|||
Active (thymidylate synthase and thymidine kinase expression) | SW620 (human colon adenocarcinoma) | 330 |
[ | |
TC-118 (colorectal tumor) | 150 mg/kg | |||
Active (ND) | Human MIA PaCa2 pancreatic tumor cells and hamster (transplanted PC-1 pancreatic adenocarcinomas) | |
[ | |
Active (effects on mevalonate and lipid metabolism) | HepG2 (hepatocellular carcinomic human cell line) |
|
[ | |
Active (high affinity with HMG-CoA reductase) | HepG2 (hepatocellular carcinomic human cell line) | ND | [ | |
Active (high affinity with HMG-CoA reductase) |
|
ND | [ | |
Active (activity of the detoxifying enzyme glutathione S-transferase) | Mucosa of the small intestine and large intestine | ND | [ | |
|
||||
|
|
|
|
|
Active (induction of apoptosis; inhibition of RhoA activation) | Hepatocarcinogenesis in rats | 25 mg/100 g | [ | |
Active (ND) | MIA PaCa2 (human pancreatic tumor cells) |
60–90%a |
[ | |
Active (nuclear factor erythroid 2-related factor-2 (Nrf2) activation) | 4NQO-induced oral carcinogenesis in mouse | 200 mg/kg | [ | |
Active (ND) |
Dual reverse virtual screening protocol |
ND |
[ |
|
|
||||
|
|
|
|
|
Active (ND) | C32 (amelanotic melanoma cell line) | 23.2 |
[ | |
Active (ND) |
HeLa (human cervical carcinoma cells) |
0.37 |
|
|
|
||||
|
Active (ND) | U2OS (bone carcinoma cells) | 21.7 |
[ |
Active (ND) | U937 (histiocytic lymphoma cell line) |
3.51 |
[ | |
Active (induction of apoptosis by activation of p53 and CDKIs) | Kasumi-1 (acute myeloid leukemia) | 49.53–127.14 |
||
HL-60 (acute myeloid leukemia) | 49.53–127.14 |
|||
THP-1 (acute myeloid leukemia) | >144.04 |
|||
U937 (acute myeloid leukemia) | >144.04 |
|||
KG-1 (acute myeloid leukemia) | >144.04 |
|||
NB4 (acute myeloid leukemia) | >144.04 |
[ | ||
K562 (blast crisis of chronic myeloid leukemia) | >144.04 |
|||
Molt-4 (acute T-lymphoblastic leukemia) | 49.53–127.14 |
|||
H-9 (acute T-lymphoblastic leukemia) | ND | |||
Jurkat (acute T-lymphoblastic leukemia) | >144.04 |
|||
Raji (human Burkitt’s lymphoma) | 49.53–127.14 |
|||
L428 (Hodgkin’s lymphoma) | >144.04 |
|||
|
||||
|
|
|
|
|
multidrug resistant MCF7 AdrR | 1.24–3.0 | |||
Active (ND) | C32 (amelanotic melanoma cell line) | 23.2 |
[ | |
Renal adenocarcinoma cells | 23.8 | |||
Active (induction of apoptosis; promotion cell differentiation) | HL-60 (acute promyelocytic leukemia cells) | ND | [ | |
Active (combination of doxorubicin-linalool increased doxorubicin influx in tumor cells) |
Mouse P388leukemia cells ( |
ND |
[ | |
Mouse P388leukemia cells ( |
1.0 mg/kg/day | |||
|
||||
|
Active (ND) | A-549 (lung carcinoma) |
43.0 |
[ |
|
||||
|
Active (ND) | MCF-7 (human breast cancer cells) | 1.3 mg/L | [ |
ND: not determined.
*Variable values refer to differences on the concentrations used, time of treatment, cell line, and/or assay used.
a% survival and/or proliferation.
b% growth inhibition.
c% mortality.
Linalyl acetate, alpha-terpineol, and camphor in association linalyl acetate, alpha-terpineol, and camphor caused inhibition of the growth of the human colon cancer cell lines (HCT-116 p53+/+ and p53−/−) and were inactive on FHs74Int normal human intestinal cell lines [
Okamura and collaborators [
Menthol was cytotoxic for murine leukemia WEHI-3 cells in a concentration-dependent manner. The
Beta-dolabrin presented
Alpha-thujaplicin inhibited cell growth of Ehrlich’s ascites carcinoma and KATO-III human stomach cancer [
The cytotoxicity of borneol and its DNA-damaging effects were studied in malignant HepG2 hepatoma cells, malignant Caco-2 colon cells, and nonmalignant human VH10 fibroblasts. Borneol showed cytotoxicity in all cell lines and did not cause DNA strand breaks at the concentrations studied. With respect to DNA-protective effects, borneol protected HepG2 and VH10 cells, but not Caco-2 cells, against H2O2-induced DNA damage [
Ascaridole exerts cytotoxic activity against different tumor cell lines (CCRF-CEM, HL60, and MDA-MB-231) [
Carvacrol produced significant cytotoxic activity against mouse leukemia P388 [
From the methanol extract of
Terpinene showed significant evidence for antioxidant activity and cytotoxic activity against mouse leukemia P388 cells [
Thymol presented cytotoxic effect against Hep-2 cells [
Studies have shown significant cytotoxic activity for thymohydroquinone in squamous cell carcinoma (SCC VII) and fibrosarcoma (FsaR) cell lines. This activity was dose dependent and more effective against tumor cells than L929 fibroblasts. Thymohydroquinone also showed a tumor inhibition rate of 52%
Thymoquinone possesses antiproliferative and proapoptotic activities in several cell lines [
Myrcene showed significant cytotoxic effects in crown gall tumors, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma [
Sobrerol showed anticarcinogenic activity during the initiation phase of DMBA-induced carcinogenesis, which was mediated through induction of the hepatic detoxification enzymes glutathione-S-transferase and uridine diphosphoglucuronosyl transferase [
Studies have demonstrated the antitumorigenic effects of limonene against pancreatic cancer and breast cancer [
Zheng and collaborators [
Yeruva and collaborators [
Stark and collaborators [
The cytotoxicity of 1,8-cineole was investigated against SK-OV-3, HO-8910, and Bel-7402 cell lines [
Perilla aldehyde showed marked antioxidant and radical scavenging activity using different model systems, including 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and beta-carotene-linoleic acid blenching assays, and also inhibited MCF-7, K562, and PC-12 cell growth in a dose- and time-dependent manner, with IC50 values that ranged from 0.25–5.0 mmol/L [
Terpinen-4-ol showed cytotoxicity against Hep G2, HeLa, MOLT-4, K-562, CTVR-1 [
Citral is cytotoxic against P388 mouse leukemia [
Carvone inhibited viability and proliferation of Hep-2 cells in a dose-dependent manner, with morphological analysis suggesting an involvement of apoptosis. In the SOS chromotest, carvone did not cause DNA damage at nontoxic doses. In the DNA repair test, a marked dose-dependent differential toxicity was observed [
Alpha- and beta-pinene showed cytotoxicity on tumor lymphocytes [
Carnesecchi and collaborators [
Citronellol exhibited weak cytotoxic effects against HL60 tumor cells [
Wright and collaborators [
Linalool showed cytotoxic effects on C32 cells [
The anticancer activity of
Badary [
Several studies have shown
7,12-Dimethylbenz[
Diethylnitrosamine
Reactive oxygen species
Reduced glutathione
N-Nitroso-N-methylurea
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
3-Hydroxy-3-methylglutaryl-CoA
Glutathione S-transferase
N-Nitrodiethylamine.
The authors declare that there is no conflict of interests regarding the publication of this paper.
This research was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).