Table 2.

The effects of phytochemicals against gastric cancer from experimental studies.

Natural Products	Phytochemicals	Study Type	Models	Mechanisms	Molecular Targets	Ref.
Fruits
Citrus reticulata Blanco extract	NA	In vitro	SNU-668 cells	Induced apoptosis	↓ Bcl-2 ↑ Bax and caspase-3	[71]
Cirsium chanroenicum	Pectolinarigenin	In vitro	AGS and MKN-28 cells	Induced autophagy and apoptosis Inhibited cell growth and proliferation	↓ p-4EBP1, p-p70S6K, and p-eIF4E, ↑ LC3-II conversion	[82]
Citrus fruits	Poncirin	In vitro	AGS cells	Induced apoptosis Inhibited cell proliferation	↑ FasL, caspase-8, caspase-3 and PARP cleavage	[70]
Black currant	Phenolic compounds	In vitro	SGC-7901 cells		NA	[113]
Blueberries	Pterostilbene	In vitro	AGS cells		↓ p-Rb, cyclin A, cyclin E, Cdk2, Cdk4, and Cdk6, ↑ caspase-2, -3, -8, and -9, PARP cleavage, p53, p2l, p27, and p16 proteins	[114]
Citrus fruits	Tangeretin	In vitro	SGC7901 cells	Inhibited radiation-mediated EMT, migration and invasion	↓ Notch-1, Jagged1/2, Hey-1 and Hes-1, ↑ miR-410	[93]
Mangosteen	α-Mangostin	In vitro	BGC-823 and SGC-7901 cells	Induced apoptosis Inhibited the cell viability	↓ STAT3, Bcl-xL and Mcl-1, ↑ cytochrome c	[72]
Mangosteen	Gartanin and TRAIL	In vitro	AGS cells	Enhanced the sensitization of AGS cells to TRAIL	↑ death receptor 5	[107]
Strawberry	NA	In vitro	SNU-638 cells	Inhibited cell growth	NA	[115]
Citrus reticulate cv. Suavissima	Poncirin	In vitro	SGC-7901 cells			[54]
Vegetables
Cruciferous vegetables	3,3’-Diindolylmethane	In vitro	BGC-823 and SGC-7901 cells	Inhibited cell proliferation Induced autophagy	↓ MicroRNA-30e, ↑ ATG5 and LC3	[83]
		In vivo	Female nude mice	Inhibited the growth of gastric tumor	↑ LC3
Cruciferous vegetables	Paclitaxel and 3,3’-diindolylmethane	In vitro	SNU638 cell	Induced apoptosis Inhibited proliferation	↑ PARP, caspase-9, ↓ CDK4, p53, cyclin D1 and p-Akt	[109]
Spices
Fruit of long pepper	Piperlongumine	In vitro	SGC-7901, BGC-823 and KATO III cells	Induced apoptosis	↓ TrxR1, ↑ ROS	[21]
		In vivo	Female BALB/cA athymic mice	Reduced tumor cell burden	↓ TrxR1
Allitridi	NA	In vitro	BGC823 cells	Induced apoptosis Inhibited cell proliferation	↓ Bcl-2, ↑ caspase-3	[52]
Allium ursinum L	NA	In vitro	AGS cells		↓ cyclin B	[56]
Garlic	Diallyl trisulfide	In vitro	AGS cells		↑ ROS, phosphorylation of AMPK and histone H3	[60]
Ginger	6-Shogaol	In vitro	HGC, AGS and KATO III cells	Inhibited cell viability Induced mitotic arrest Damaged microtubules	NA	[64]
		In vivo	Athymic nude mice	Suppressed tumor growth	NA
Ginger	Zerumbone	In vitro	AGS cells	Anti-angiogenesis	↓ VEGF and NF-κB	[89]
Ginger	6-Gingerol and cisplatin	In vitro	HGC-27 cells	Inhibited cell proliferation, migration and invasion	↑ P21 and P27, ↓ cyclin D1, cyclin A2, MMP-9, p-PI3K, Akt, and p-Akt	[112]
Curcuma zedoaria rhizomes	Curcuzedoalide	In vitro	AGS cells	Induced apoptosis Inhibited cell viability	↑ cleavage of caspase-8, caspase-9, caspase-3 and PARP	[116]
Curcuma mangga rhizomes	Labdane diterpenes	In vitro	AGS cells	Inhibited cell proliferation	NA	[53]
Turmeric	Curcumin, etoposide and doxorubicin	In vitro	SGC-7901 cells	Enhanced the anticancer efficacy of etoposide and doxorubicin	↓ NF-κB, Bcl-2 and Bcl-xL	[10]
Garlic	Diallyl trisulfide and docetaxel	In vitro	BGC823 cells	Induced apoptosis Induced G2/M cell cycle arrest	↑ MT2A, IκB-α, cyclin B1, activated caspase-3, and Bax, ↓ p-IκB-α, p-P65, cyclin D1, and XIAP	[110]
		In vivo	Female BALB/c athymic mice	Inhibited tumor growth	↑ MT2A, IjB-a, CCNB1, and a-CASP3, ↓ CCND1
Garlic	Diallyl disulfide	In vitro	MGC803 cells	Inhibited cell growth Induced cell differentiation	↓ CDC25C, cyclin B1, p-ERK1/2, ↑ p-Chkl	[57,59]
Garlic	Diallyl disulfide	In vitro	AGS cells	Inhibited tumor cell motility and invasion	↓ MMP-2, MMP-9, claudin proteins (claudin-2, -3, and -4), ↑ TIMP-1, TIMP-2	[94]
Garlic derivatives	S-allylmercaptocysteine	In vivo	Female BALB/c nude mice	Inhibited the growth of gastric tumor	NA	[63]
Zanthoxylum nitidum (Roxb) DC	Nitidine chloride	In vitro	SGC-7901 and AGS cells	Induced apoptosis Inhibited cell viability and angiogenesis	↓ p-STAT3, cyclin D1, Bcl-2, Bcl-xL, and VEGF	[23]
		In vivo	Male BALB/cA nude mice	Reduced the volume of tumors	↓ STAT3 and VEGF
Mushroom
Liang Jin mushroom	3’-azido-3’-deoxythymidine (AZT) and RNA-protein complex (FA-2-b-β)	In vitro	MKN-45 cells	Induced apoptosis Inhibited cell proliferation	↓ tumor cell telomerase and Bcl-2, ↑caspase-3	[117]
Agaricus blazei Murrill	Blazein	In vitro	KATO III cells	Induced apoptosis Suppressed cell growth	NA	[118]
Phellinus linteus	Polyphenol compound hispolon	In vitro	SGC-7901, MGC-803, and MKN-45 cells	Induced apoptosis	↓ Bcl-2, ↑ ROS, cytochrome c, caspase-3 and caspase-9	[74]
Hericium erinaceus mycelium	Erinacine A	In vitro	TSGH9201 and MKN-28 human gastric cancer cells	Induced apoptosis Inhibited the viability and invasiveness	↓ Bcl-2 and Bcl-XL, ↑ ROS, MTUS2, TRAIL, caspase 8, caspase 9, caspase 3, cytochrome c and phosphorylation of FAK/Akt/p70S6K and PAK1	[91]
Lentinula edodes C91-3	Latcripin 1 protein	In vitro	SGC-7901 and BGC-823 cells	Induced autophagy and apoptosis Inhibit cell growth and proliferation	↓ Bcl-2, MMP-2 and MMP-9, ↑ Bax, caspase-3, ATG7, ATG5, ATG12, ATG14 and Beclin1	[61]
Ganoderma lucidum	NA	In vitro	AGS cells		↑ LC3-II	[119]
	Recombinant Lz-8 protein	In vitro	SGC-7901 cells	Induced autophagic cell death Inhibited cell growth	↑ CHOP, ATF4 and GRP78	[120]
Fomes Fomentarius	Polysaccharide	In vitro	SGC-7901 and MKN-45 cells	Inhibited cell proliferation	NA	[20]
Maitake (Grifola frondosa)	NA	In vitro	TMK-1, MKN-28, MKN-45 and MKN-74 cells		NA	[121]
Soy
Black soybean	NA	In vitro	AGS cells	Induced apoptosis Inhibited cell proliferation	↓ Bcl-2, ↑ Bax, caspase-3, PARP cleavage	[75]
Soy products	Genistein, fluorouracil and ciplatin	In vitro	MGC-803 cells	Decreased chemoresistance	↓ ABCG2, ERK1/2	[108]
Traditional medicine
Gardenia jasminoides Ellis	Carotenoids	In vitro	MKN-28 cells	Inhibited cell proliferation	NA	[122]
Perilla frutescens	Perillaldehyde	In vitro	MFCs and GC9811-P cells	Induced autophagy	↑ p-AMPK	[84]
		In vivo	Female BAL B/c nude mice	Inhibited the growth of gastric tumor Induced autophagy	↑ beclin-1, LC3-II, cathepsin, caspase-3 and p53
Vitex agnus-castus fruit	NA	In vitro	KATO-III Cells	Induced apoptosis	↓ Bcl-2, Bcl-XL, Bid, Mn-superoxide dismutase and catalase, GSH, ↑ Bad, cytochrome c, caspase-3 caspases-8, caspases-9, hemeoxygenase-1 and thioredoxin reductase	[73]
Bamboo shavings	Polysaccharides	In vivo	Syngeneic murine gastric cancer model	Inhibited tumor growth Prolonged the survival	↑ cleaved caspase 3, Bax and Bik	[79]
Other
	Protocatechuic acid	In vitro	AGS cells	Induced apoptosis Inhibited cell proliferation	↓ cyclin B, ↑ JNK and p38 MAPK	[69]
	Kaempferol	In vitro	AGS, NCI-N87, SNU-638 and MKN-74 cells	Induced autophagic cell death Decreased cell viability	↓ p62, ↑ LC3B, Beclin-1, ATG5, p-IRE1 and p-JNK	[22]
	Myricetin	In vitro	HGC-27 and SGC7901 cells	Inhibited cell proliferation	↑ Mad1	[62]
	Apigenin	In vitro	SGC-7901 cells	Inhibited cell growth	NA	[55]
	Luteolin	In vitro	Hs-746T and MKN-28 cells	Induced cell apoptosis Inhibited cell proliferation, invasion, and migration	↓ Notch1	[92]
		In vivo	Male BALB/c nude mice	Reduced gastric tumor volume and tumor weight	↓ β-catenin, Notch1 and Ki-67
	Gallic acid	In vitro	AGS cells	Inhibited cell metastasis	↓ MMP-2, MMP-9, NF-κB, Ras, Cdc42, Rac1, RhoA, RhoB and PI3K	[90]
	Luteolin	In vitro	MGC-803 and Hs-746T cells	Anti-angiogenesis Inhibited the formation of vasculogenic mimicry tube	↓ VEGF and Notch1	[88]
	Quercetin and SN-38 (a metabolite of irinotecan)	In vivo	Female BALB/c nude mice	Reduced the volume of tumors Anti-angiogenesis and anti-metastasis	↓ cyclooxygenase-2, Twist1, ITGβ6, VEGF-R2 and VEGF-A	[24]
		In vitro	AGS cells	Induced apoptosis	↓ β-catenin

NA: not available.