TABLE 1.

The effects of Zataria multiflora and Nigella sativa and their derivatives, carvacrol and thymoquinone, on lung cancer.

Study type	Type of lung cancer	Preparations	Dose	Effects	Ref.
	A549 cell	CN	0–150 μg/mL	Decreased MAPK p38, ERK activation, COX‐2 and VEGF expression	39
	NSCLC	Carvacrol	0, 30, 100 and 300 μM	Decreased AXL protein expiration, inhibited AXL phosphorylation	44
	NSCLC	Carvacrol nanoemulsion	25, 50 and 100 μg/mL	Decreased ROS, regulated p‐JNK, Bax, Bcl2, increased Cyt c, caspase, apoptosis, down‐regulated CHOP, p‐eIF2α, GRP78 expression	43
	NSCLC	Carvacrol	100–1000 μM	Decreased morphology changes, cell growth	42
	Doxorubicin resistant‐A549 cell line	Carvacrol nanoemulsion	5, 25 and 50 μg/mL after 24 h	Elevated Bax, Cyt c, cleaved caspase 3 and 9, p21 protein expression, reduced CDK2, CDK4, CDK6, Cyclin E, cyclin D1	43
	NCI‐H460 cells	TQ	1.25, 0.5, 5 μM, for 24, 48 and 72 hrs	Reduced cell proliferation, cytokines expression, ENA‐78, GRO‐alpha, increased apoptosis level, cell viability	47
	NSCLC	TQ	10, 20, 40 μmol/L	Inhibited cell proliferation, migration PCNA, cyclin D1, MMP2, MMP9 mRNA, activation ERK1/2 pathway, cell cycle	55
	A549 non‐small cell	TQ	2, 5, 10 μM	Up‐regulated Bax, p21, receptor 1 and 2 expressions, Bax/Bcl2 ratio, down‐regulated Bcl2 proteins, inflammatory markers, ROS, cyclin D, NF‐kappa B and IKK1 expression	56
In vivo	Tumour‐bearing BALB/c mice	Z. multiflora Essential oil	500 mg/kg	Increased TNF‐α, IFN‐γ, IL‐2, decreased IL‐4 level	38
	Lung cancer induced‐B(a)P	Carvacrol	25 and 50 mg/kg, 7 days	Enhanced antioxidants, iNOS, NF‐κB and COX‐2 expressions, decreased positive stained cells	40
	Lung cancer model (athymic nude mice)	Carvacrol	50 and 100 mg/kg	Reduced tumour growth and weight, increased p‐JNK, Bax, Bcl2, Cyt C, caspase‐3, caspase‐9 and β‐ Actin expression	43
	Rat multi‐organ carcinogenesis	N. sativa volatile oil	1000 or 4000 ppm, 30 weeks	Reduced carcinogenesis incidences, multiplicities	54
	Lung cancer model of mice	TQ	5, 20 mg/kg	Decreased tumour volume and weight, NF‐KB	47
	CD1‐nude mice	TQ	5, 10, 10 mg/kg	Reduced p‐AKT, p‐mTOR, caspase‐3, p‐53, NF‐κB expression	58
	B(a)P‐induced rat's lung cancer	TQ	50 mg/kg b.w.	Decreased NFk‐B expression, ROS, MDA, NO, increased apoptosis, CAT and SOD activities	62

Abbreviations: B(a)P, benzo(a)pyrene; CN, carvacrol nanoemulsion; IFN‐γ, interferon‐gamma, IL‐2, interleukin‐2; NF‐κB, nuclear factor kappa B; NSCLC, non‐small cell lung cancer; NSE, seed extract; Ref, references; ROS, reactive oxygen species; SPBP, soy‐phospholipid‐based phytosomes; TNF alpha, tumour necrosis factor‐alpha; TQ, thymoquinone; VEGF, vascular endothelial growth factor.