Essential Oils and Their Constituents as Anticancer Agents: A Mechanistic View

Table 4

List of EO constituents studied for anticancer potential in both in vitro and in vivo models, and major observations reported.

Constituents used	Model systems used	Major findings/mechanism(s) reported	Reference
Azadirachtin and nimbolide	Hamster buccal pouch (HBP) carcinogenesis model	Cell cycle arrest and apoptosis by intrinsic and extrinsic pathway	[172]
Azadirachtin and nimbolide	Hepatocarcinoma (HepG2)	G0/G1 phase cell cycle and apoptosis via ROS induction and cytochrome C release in mitochondria	[173]
Azadirachtin and nimbolide	Hamster buccal pouch (HBP) carcinogenesis model	Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cancer, prevention of procarcinogen activation and oxidative DNA damage, upregulation of antioxidant and carcinogen detoxification enzymes, inhibition of tumour invasion and angiogenesis	[174]
Carvacrol	Male wistar albino rats with liver cancer induced by diethylnitrosamine (DEN)	Chemoprevention	[29]
Carvacrol	Human cervical cancer cell lines (HeLa and SiHa)	Apoptosis	[175]
Carvacrol	K-562, P-815, CEM, MCF-7 and MCF-7 gem (gemcitabine resistant)	Arrest in S-phase progression	[39]
Carvacrol	Liver cancer (HepG2) cell line	Apoptosis via activation of caspases and mitogen-activated protein kinase (MAPK) pathway	[176]
Carvacrol	Lung cancer (A549) cell line	Growth inhibition	[177]
Carvacrol	Human metastatic breast cancer (MDA-MB 231) cell line	Apoptosis	[178]
Carvone	Primary rat neuron and neuroblastoma (N2a) cells	Increase in antioxidant level in primary cells with little potential in treatment of brain tumour	[179]
Citral	Breast cancer (MCF-7) cell line	G2/M phase arrest and apoptosis	[41]
Citronellal and synthetic analog C37A (N-citronellylamine)	Human breast cancer (MCF-7) and a non-tumorigenic (Vero) cell line	Cytotoxicity	[114]
D-limonene	Colon cancer (LS174T) cells	Apoptosis by inactivation of akt pathway	[180]
Elemene	Laryngeal cancer (Hep-2) cells	Growth inhibition via decrease in eIF4E, eIF4G, bFGF and VEGF	[181]
Elemene	Colon cancer (Lovo) cells	Inhibition of telomerase activity, cell cycle arrest, and apoptosis	[182]
Eugenol	Primary melanoma (Sbcl2), radial growth phase (WM3211), primary RGP, radial and vertical growth phase (WM98-1), primary RGP and VGP, Lu-metastatic melanoma (WM1205) and Female B6D2F1 mice with B16 melanomas	Suppresses melanoma via deregulation of the E2F1 transcription factors	[183]
Eugenol	N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced gastric cancer in rat	Tumour reduction by suppression of NF-κB activation	[184]
Eugenol	Breast cancer (MCF-7) cells	Growth inhibition and apoptosis induction with decrease in levels of intracellular antioxidants	[184]
Eugenol	Androgen-insensitive prostate cancer cells (DU-145) and oral squamous carcinoma (KB) cells	Eugenol and its synthetic analogues inhibited growth without losing membrane integrity	[185]
Eugenol	Human colon cancer (HT-29) cells	Suppression of cyclooxygenase-2 activity and growth	[186]
Eugenol	Colon cancer (HCT-15 and HT-29) cells	Induction of ROS leading to apoptosis	[187]
Eugenol	Human promyelocytic leukemia (HL-60) cells	Induction of ROS, mitochondrial permeability transition (MPT), reduction of bcl-2 level, cytochrome c release leading to apoptosis	[165]
Eugenol	Human Melanoma (G361) cell line	S-phase cell cycle arrest and apoptosis	[188]
Furanodiene	Liver cancer (HepG2) cell line	G2/M phase arrest and apoptosis via inhibition of MAPK signalling pathway	[189]
Geraniol	Human colon cancer (Caco) cell line	Enhances sensitivity to 5-fluorouracil treatment	[32]
Geraniol	Human colon cancer (Caco) cell line	Inhibits growth and Polyamine biosynthesis-mechanism of inhibition of proliferation	[31]
Geraniol	Human colon cancer (Caco) cell line	Membrane depolarisation, decreased activity of protein kinase C activity and p44/p42 extracellular signal-regulated protein kinases (ERK)	[190]
Geraniol	Human tumours (TC-118) induced in Swiss nu/nu mice	Reduction in thymidylate synthase and thymidine kinase expression, synergistic effect of geraniol with 5-fluorouracil	[33]
Germacrene D	Murine melanoma (B16F10-Nex2), human glioblastoma (U-87 MG), cervical carcinoma (HeLa), leukemia (HL-60), colon carcinoma (HCT), breast adenocarcinoma (SKBr), and melanoma (A2058); and non-tumorigenic (HFF) cell lines	Cytotoxicity	[116]
Neem oil limonoids	Colon cancer (HCT116 p53−/−, HCT116 p21−/−) LNCaP, PPC1 and MDA-MB231 cell lines	p53 independent apoptosis autophagy	[191]
Nimbolide	Colorectal cancer (CRC) cell lines and CRC xenografts in nude mouse model	Apoptosis by caspase activation and PARP cleavage and decrease in tumour size in xenograft models	[192]
Nimbolide	Human hepatocarcinoma (HepG2)	Bcl-2, Bax, cytochrome-c, Smac/DIABLO, caspase-3, and caspase-9 activation leading to intrinsic pathway for apoptosis NF-κB signaling	[193]
Nimbolide	Colon cancer (WiDr) cells	S-phase cell cycle arrest and caspase-mediated apoptosis	[194]
Patchouli alcohol	Human colorectal cancer (HCT 116, SW480) cells	NF-κB, p 21 activation and suppression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) resulting in apoptosis and decreased growth	[65]
Perillyl alcohol	Human colon carcinoma (HCT 116) cell line	Dose dependent inhibition attributed to G1 arrest	[70]
Perillyl alcohol	Female BALB/c mice	Tumour inhibition	[195]
Perillyl alcohol	BALB/c mice	UV-B induced AP-1 trans-activation inhibition and reduction of the tumours	[60]
Perillyl alcohol	Lung cancer (A549 and H520) cell lines	Cell cycle arrest and apoptosis	[196]
Terpinen-4-ol	Murine mesothelioma (AE17), melanoma cells (B16-F10), and fibroblasts (L929)	Necrotic cell death and apoptosis to lower extent in cancer cells	[197]
Thymol	Human promyelocytic leukemia (HL-60) cells	Caspase-dependent and independent apoptosis	[40]
Thymol	Human liver cancer (Bel-7402) cells	Antiproliferative activity	[198]
Thymol	K-562, P-815, CEM, MCF-7, and MCF-7 gem	Prevention of G0/G1 phase transition	[39]
Thymoquinone	Human colon cancer (LoVo, HCT 116, Caco-2, HT-29 and DLD-1) and human intestinal (FHs74Int) cells	ROS generation and mitogen-activated protein kinases (MAPK) JNK and ERK activation in cancer cells leading to apoptosis	[199]
Trans-caryophyllene	Breast cancer (MCF-7), colon cancer (HCT-116) and murine macrophage (RAW264.7) cell lines	Cytotoxicity	[134]
𝛼-humulene	Breast cancer (MCF-7), colon cancer (HCT-116) and murine macrophage (RAW264.7) cell lines	Cytotoxicity	[134]
𝛼-santalol	Breast cancer (MCF-7 and MDA-MB-231) cells	G2/M phase cell cycle arrest and apoptosis with little effect on normal breast cells	[200]
𝛽-caryophyllene	Human tumour (MCF-7, DLD-1 and L-929) cell lines	Enhanced activity of α-humulene, isocaryophyllene, and paclitaxel	[38]
𝛽-Caryophyllene oxide	Human prostate (PC-3) and breast cancer (MCF-7) cells	ROS generation and PI3K/AKT/mTOR/S6K1 signaling activation leading to apoptosis	[201]
𝛽-elemene	Lung cancer (H460 and A549) cells	G2-M phase cell cycle arrest	[71]
𝛽-elemene	Melanoma (B16F10) cells	Inhibition of angiogenesis via VEGF factor, antiproliferative and antimetastatic activity	[73]
𝛽-elemene	Human breast cancer (MCF-7/ADM) cell line	Enhancement of adriamycin effect at its nontoxic concentration	[202]
𝛽-elemene	G-422 tumour cells in mice	Cross blood brain barrier and inhibit brain carcinomas	[203]
𝛽-elemene	Lung cancer (A549) cells	PI3K/Akt/mTOR/p70S6K1 signaling pathway inhibition and induces autophagy	[204]
𝛽-elemene	Human ovarian cancer (A2780 and A2780/CP) cell lines	G2-M cell cycle arrests, cyclin B1 and Cdc2 downregulation and elevation of p53, p21waf1/cip1, p27kip1 and Gadd45 levels	[205]
𝛽-elemene	Liver cancer (HepG2) cells	G2/M phase cell cycle arrest and apoptosis	[206]
𝛾-humulene	Colorectal cancer (HT29) cells	Apoptosis via upregulation of the CD95 receptor and CD95L on cell surface	[207]