Table 1.

Essential oil phenylpropanoids with antitumoral activity.

Compound	Experimental protocol	Antitumoral activity and/or mechanism	Animal/cell line tested	Reference
	Anaphylaxis model	Apoptotic manifestations via phospho-ser 15-p53 into mitochondria	Mast cells	[11]
	Skin carcinogenesis model	Inhibition of the proliferation associated genes c-Myc and H-ras and antiapoptotic gene Bcl2 along with upregulation of proapoptotic genes Bax, p53, and active caspase-3	Mice	[12]
	Trypan-blue assays	Cytotoxic activity	B16-F10, Sbcl2, WM3211, WM98-1 and WM1205Lu, PC-3, human gingival fibroblasts, oral mucosal, neutrophils—male guinea pig, rat hepatocytes cells	[14, 15, 23, 32, 33, 48, 49]
	Melanoma cell proliferation	Deregulation of the E2F family of transcription factors, transcriptional activity of E2F1	Sbcl2, WM3211, WM98-1, and WM1205Lu cells	[15]
	Flow cytometry analysis	Cytotoxic activity	P-815, K-562, CEM, and MCF-7 cells	[13]
	VL irradiation time	Antioxidative reactivity	HSG, HSC-2, and HL-60 cells	[17]
	MTT assay	Cytotoxic activity	B16-F10, P-815, K-562, CEM, MCF-7, MCF-7 gem, HeLa, DU-145, KB, HSG, human dental pulp, murine peritoneal macrophages HL-60, HepG-2, B16, cells	[13, 19–22, 25–29, 38, 45, 46, 48]
	DPPH assay	Antioxidative activity	Caco-2 cells and VH10 fibroblasts	[18]
	Flow cytometer analysis	Enhanced the accumulation of cells in the S and G2/M phase which may be unable to divide	HeLa cells
	DAPI staining	Increase in the number of apoptotic cells
	In vitro hemolytic activity	Hemolytic activity	Human erythrocytes	[19]
	Caspase-3 colorimetric assay	Induce caspase 3-mediated apoptosis
	RT-PCR	Anticancer activities via apoptosis induction and anti-inflammatory downregulation of Bcl-2, COX-2, and IL-1β
	RT-PCR	Downregulated the expression of Bcl-2, COX-2, and IL-β	HeLa cells	[20]
	Flow cytometer analysis	Increased population of cells G2/M phase by 4.5-fold	PC-3 cells	[24]
	Western blot and RT-PCR analysis	Reduced expression of antiapoptotic protein Bcl-2 and enhanced expression of proapoptotic protein Bax
	DPPH radical-scavenging activity	Formation of dimers	HSG cells	[25]
	ELISA	Reduced the nicotine-induced ROS, NO generation, and iNOSII expression	Murine peritoneal macrophages	[27]
	Spectrophotometric analysis	Increase in LDH release	DU-145 and KB cells	[28]
	ESR analysis	Activity of the production of phenoxyl radicals with most efficiently scavenged reactive oxygen	HSG cells	[29]
	Laser cytometry analysis	Production of ROS induced by VL-irradiated is significantly affected by pH
	Antioxidants production	Produced antioxidants in alkaline solutions	Human salivary gland and oral squamous cells	[30]
	DPPH assay	Apoptosis-inducing effect	HGF and HSG cells	[31]
	TBA analysis lipid oxidation	Depleted intracellular glutathione; protect cells from the genetic attack of reactive oxygen species via inhibition of xanthine oxidase activity and lipid peroxidation	Oral mucosal fibroblasts	[32]
	ATP assay	Decreased cellular ATP level in a concentration- and time-dependent manner
	NR assay	Intracellular glutathione levels	HFF and HepG2 cells	[33]
	Dichlorofluorescein assay	Reduction in the intracellular level of GSH	HSG cells	[34]
	CAs assay	Induced a dose-dependent increase of aberrant cells	V79 cells	[41]
	Topo II activity assay	Inhibition of topoisomerase II
	Croton oil induced skin carcinogenesis	Inhibition of the proliferation associated genes c-Myc and H-ras and antiapoptotic gene Bcl2 along with upregulation of proapoptotic genes Bax, p53, and active caspase-3	Swiss mice	[36]
	DMBA/TPA-induced carcinogenesis in murine skin	Declined of hyperplasia, epidermal ODC activity, and protein expression of iNOS, COX-2, and secretion of proinflammatory cytokines	Swiss mice	[42]
	TUNEL assay	Upregulation of p53 expression with a concomitant increase in p21WAF1 levels in epidermal cells indicating induction of damage to the DNA
	Flow cytometric analysis	cDNA array analysis showed that eugenol caused deregulation of the E2F family of transcription factors	WM1205Lu cells	[24]
	TUNEL assay	Induces apoptosis in melanoma tumors	WM1205Lu cells
	DPPH assay	Antioxidative properties	HL-60 and HepG-2 cells	[48]
	Sulforhodamine B assay	Cytotoxic activity	SK-OV-3, XF-498, and HCT-15 cells	[76]
	Murine Ehrlich ascites and solid carcinoma models	Inhibit the growth of Ehrlich ascites	BALB/c mice	[44]
	DPPH assay	Antioxidation activity	HepG2 cells	[22]
	Western blot analysis	Decreased the protein expression of BSP in a concentration-dependent manner	Human dental pulp cells	[35]
	DPPH assay	Antioxidant effect	Raw 264.7 cells	[43]
	VL irradiation/MTT assay	Generation of eugenol radicals	HSG and HGF cells	[36]
	Laser cytometer	Generation of ROS
	ESR analysis	Produced phenoxyl radicals	HSG and HGF cells	[37]
	Superoxide generation/spectrophotometer	Stimulation the production of superoxide (O2 −)	Neutrophils—male guinea pig	[40]
	DPPH assay	Antioxidative properties	HL-60 and HepG-2 cells	[48]
	UDS assay	Cytotoxicity and genotoxicity effects	B6C3F1 mouse hepatocytes	[47]
			F-344 rat hepatocytes
	L-Lactate assay	Cytotoxic effect	B6C3F1 mouse hepatocytes
			F-344 rat hepatocytes
	MTT assay DPPH assay	Cytotoxic activity Antioxidative properties	HL-60, HepG-2, WM266-4, SK-Mel-28, LCP-Mel, LCM-Mel, PNP-Mel, CN-MelA, and GR-Mel cells	[16, 48]
	WST assay SRB assay	Cytotoxic and genotoxic properties	V79 cells	[49]
	Corn oil gavage	Carcinogenic activity is based on increased incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatocellular adenoma or carcinoma (combined)	F344/N rats and B6C3F1 mice	[50]
	Trypan-blue exclusion assay	Cytotoxic activity	Rat hepatocytes	[55]
	MTT assay	Cytotoxic activity	HSG cells	[29]
	DPPH radical-scavenging activity	Cormation of dimers
	Dichlorofluorescein assay	Reduction in the intracellular level of GSH		[39]
	MTT assay	Inhibition of cell proliferation	WM266-4, SK-Mel-28, LCP-Mel, LCM-Mel, PNP-Mel, CN-MelA, and GR-Mel cells	[16]
	WST assay SRB assay	Cytotoxic and genotoxic properties	V79 cells	[49]
	L-Lactate assay	Cytotoxic effect	B6C3F1 mouse hepatocytes	[47]
			F-344 rat hepatocytes
	UDS assay	Cytotoxicity and genotoxicity effects	B6C3F1 mouse hepatocytes
			F-344 rat hepatocytes
	Trypan-blue exclusion assay	Potential cytotoxic effects	Rat hepatocytes and SCC-4 cells	[47, 51, 54]
	Flow cytometric assay	Induction of apoptosis of cells by involvement of mitochondria- and caspase-dependent signal pathway	SCC-4 cells	[51]
	Western blotting analysis	Upregulation of the protein expression of Bax and Bid and downregulation of the protein levels of Bcl-2 (upregulation of the ratio of Bax/Bcl-2), resulting in cytochrome c release, promoted Apaf-1 level, and sequential activation of caspase-9 and caspase-3 in a time-dependent manner
	Real-time PCR	mRNA expressions of caspases 3, 8, and 9
	MTT assay	Cytotoxic effect	Human BMFs	[52]
	Western blot analysis	Activate NF-κB expression that may be involved in the pathogenesis of OSF and mediated by ERK activation and COX-2 signal transduction pathway
	Fura-2 as a probe assay	Induced a [Ca2+]i increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion and by inducing Ca2+ influx	PC3 cells	[53]
	Comet assay/(DAPI) staining	Induced apoptosis (chromatin condensation) and DNA damage	HL-60 cells	[51]
	Flow cytometric analysis	Increased the production of reactive oxygen species (ROS) and Ca2+ and reduced the mitochondrial membrane potential
	Western blotting analysis/confocal laser microscopy	Promoted the expression of glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), and activating transcription factor 6α (ATF-6α)
	Flow cytometric analysis	Promoted the levels of CD11b and Mac-3 that might be the reason for promoting the activity of phagocytosis; reduced the cell population such as CD3 and CD19 cells	NK cells	[58]
	Ames test	Mutagenicity activity	Salmonella TA 98	[59]
	MTT assay	Produced toxicity in cells in a dose- and time-dependent manner	HepG2 cells FVB mice	[56]
	Comet assay	Significant dose-dependent increase in the degree of DNA (strand breaks)
	Cytotoxic or genotoxic effect in vivo—i.p./Comet assay	Increase in mean Comet tail moment in peripheral blood leukocytes and in the frequency of micronucleated reticulocytes	HepG2 cells FVB mice
	TUNEL assay	Activity of caspases 3, 8, and 9	A549 cells	[58]
	Western blot assay	Cleavages of PARP, accompanied by an accumulation of cytochrome c and by the activation of caspase-3	SK-N-SH cells	[60]
	Induction of GST and QR	Induction of GST and QR in mouse livers	Four strains of mouse: A/JOlaHsd, C57BL/6NHsd, BALB/cAnNHsd, and CBA/JCrHsd	[61]
	Trypan-blue exclusion assay	Cytotoxic activity	Rat hepatocytes	[55]
	Trypan-blue assay	Cytotoxic activity	HeLa, rat hepatocytes cell	[21, 23, 55, 64]
	MTT assay	Cytotoxic activity	HT-1080, ML1-a cells	[63]
	Boyden-chamber assay	Reduced 40 and 85% of cells to invade into Matrigel	HT-1080 cells	[62]
	Gelatin zymography and RT-PCR analyses	Inhibitory effect of MMP-2 and MMP-9 and downregulate the expression of matrix metalloproteinases (MMPs) 2 and 9 and upregulate the gene expression of tissue inhibitor of metalloproteinase- (TIMP-) 1
	Expression of MMPs, TIMPs, and uPA assays	Decreased mRNA expression of urokinase plasminogen activator (uPA)
	Western blot analysis	Suppressed the phosphorylation of AKT, extracellular signal-regulated kinase (ERK), p38, and nuclear transcription factor kappa B (NF-κB)
	Fluorometric assay	Increases in the levels of ADP and AMP	Rat hepatocytes	[62]
	CCK-8 assay	Estrogenic effect based on the concentrations of the hydroxylated intermediate, 4OHPB	MCF-7 cells
	Western blot analysis	Suppressed TNF-induced activation of the transcription factor AP-1, c-jun N-terminal kinase, and MAPK-kinase	ML1-a cells	[63]
	Colorimetric e fluorometric assays	Reduced the levels of nucleic acids and MDA, and increased NP-SH concentrations	EAT cells in the paw of Swiss mice	[65]
	Ames test	Mutagenic for Salmonella tester strains	Salmonella typhimurium strains TA1535, TA100, and TA98
	Induction of hepatic tumors	Carcinogenic in the induction of hepatomas	B6C3F1 mice	[67]
	Induction of skin papillomas	Carcinogenic in the induction of skin papillomas	CD-1 mice
	SRB assay	Cytotoxic activity	A549, SK-OV-3, SK-MEL-2, and HCT15 cells	[70]
	Ames test	Mutagenic for Salmonella tester strains	Salmonella typhimurium strains TA1535, TA100, and TA98
	Induction of hepatic tumors	Carcinogenic in the induction of hepatomas	B6C3F1 mice	[67]
	Induction of skin papillomas	Carcinogenic in the induction of skin papillomas	CD-1 mice
	MTT assay	Cytotoxic activity	A375, HCT 116, MCF-7, P388, L-1210, 3LL, SNU-C5, HL-60, U-937, HCT 116, L1210 mouse, and Syrian hamster embryo cells	[71, 77, 78, 80, 84, 89]
	TRPA1 and TRPM8 gene expression	Reduce the proliferation of melanoma cells; this effect is independent of an activation of TRPA1 channels	A375, G361, SK-Mel-19, SK-Mel-23, and SK-Mel-28 cells	[77]
	Sulforhodamine B assay	Cytotoxic activity	HeLa, A549, SK-OV-3, SK-MEL-2, XF-498, and HCT-15 cells	[76]
	Ames test	Not mutagenic	Strains (TA 98, TA 100, TA 1535, and TA 1537) of Salmonella typhimurium
	DTNB assay	TrxR inactivation	Recombinant rat TrxR	[78]
	Western blot analysis	Induced an adaptive antioxidant response through Nrf2-mediated upregulation of phase II enzymes, including TrxR induction	HCT 116 cells
	XTT assay	Inhibitory effects on the growth of cells	Hep G2 cells	[80]
	Western blot analysis	Increase in the CD95 (APO-1/CD95) protein expression in Hep G2 cells
		Inhibited the expression of Bax, p53, and CD95, as well as the cleavage of PARP. This pretreatment also prevented the downregulation of Bcl-XL in cells
	Trypan-blue assay	Inhibited the proliferation of cells	PLC/PRF/5 cells	[81]
	Flow cytometer analysis	Activation of proapoptotic Bcl-2 family (Bax and Bid) proteins and MAPK pathway	PLC/PRF/5 cells	[83]
	Western immunoblot analysis	Prevented the phosphorylation of JNK and p38 proteins
	DAPI/Fluorometric method	Induced apoptosis in cells	P388, L-1210, 3LL, SNU-C5, HL-60, U-937, and HepG2 cells	[71]
	Flow cytometry analysis	Induces the ROS-mediated mitochondrial permeability transition and resultant cytochrome c release
	cis-DDP-induced	Potentiated the inactivating effect of cis-DDP in all phases of the cell cycle	NHIK 3025 cells	[82]
	NRU assay	Induced the fragmentation of nuclei (Plate 2), which is typical for condensed apoptotic phenotype	Hep-2 cells	[87]
	Genotoxicity assays—DNA repair test	Involve DNA damage as one of the factors involved in the mammalian cytotoxicity
	LDH-cytotoxicity assay	Potent inhibitory effect against human hepatoma cell growth	HepG2 and Hep3B cells	[88]
	Western blot analysis	JAK2-STAT3/STAT5 pathway may be important targets
		Decreased the protein levels of cyclin D1 and proliferative cell nuclear antigen (PCNA) but increased the protein levels of p27Kip1 and p21Waf1/Cip1
	Flow cytometry analysis	Inducing apoptosis and synergizing the cytotoxicity of CIK cells	K562 cells	[92]
	Spectral analysis	Induced an adaptive antioxidant response through Nrf2-mediated upregulation of phase II enzymes, including TrxR induction	S180 in mice	[89]
	MTT assay	Cytotoxic activity	NIH/3T3 cells	[90]
	Lymphoproliferation—Con A, LPS, or PMA plus ionomycin	Inhibit the lymphoproliferation and induce a T-cell differentiation from CD4CD8 double positive cells to CD4 or CD8 single positive cells	Mice splenocytes	[74]
	Flow cytometry analysis	Capability to block the cell growth and stimulate a differentiation to mature cell
	IgM-secreting B cells to SRBC	Decreased level of IgM to be due to the lower level of B-cell proliferation	Balb/c mice
	ELISA	Inhibits proliferation and DNA synthesis	Caco-2 cells	[79]
	Radioimmunoassay	Decreased intracellular cAMP levels
	Flow cytometry analysis	Influence on the tumor cell cycle: G2-M period shortened, cell cycle lengthened, and cell proliferation inhibited	U14 cells	[92]
	cis-DDP-induced	Potentiated the inactivating effect of cis-DDP in all phases of the cell cycle	NHIK 3025 cells	[82]
	Trypan-blue assay	Anticancer activity	HL-60, A549, PC3, Du145, LN-CaP, A172, U251, SKMEL28, and A375 cells	[93, 94]
	Flow cytometry analysis	Inhibition and induced-differentiation on human osteogenic sarcoma cells	Human osteogenic sarcoma cells	[95]
	MTT assay	Cytotoxic activity	HepG2 cells	[97]
	Spectrophotometer	Higher antioxidant capacity
	NRU assay	Cytotoxic activity	Mac Coy cells	[96]
	MTT assay	Antiviral activity	EHV-1	[98]
	Trypan-blue assay	Cytotoxic activity	Rat hepatocytes	[54]
	Waters chromatograph	Decrease in cell viability, accompanied by losses of ATP, GSH; increase in GSSG, ROS, and MDA levels
	Indirect immunofluorescent method/EBV activation	Inhibiting the generation of anions during tumor promotion	Raji cells	[100]
	Trypan-blue exclusion assay	Cytotoxic activity	RPMI8226, U266, and IM-9 cells	[99]
	Flow cytometry	Induced caspases 3, 9, and 8 activities	RPMI8226 cells
	Western blot analysis	TNF-α-induced apoptosis
	ELISA	Downregulation of NF-κB activity
		TNF-α-induced apoptosis
	In vivo assay	Anticancer effects with no toxic effects	NOD/SCID mouse