Table 2.

Anti-cancer effects of galangin based on In vitro studies.

Type of Cancer	Cell lines	Effects	Mechanisms	Concentration	References
Glioblastoma	U87, U251 and U87-luciferase	Induces apoptosis	↓ GBM cell growth, migration, and invasion, ↓ Skp2, ↓ Zeb1, ↓ N-cadherin, ↓ snail, ↓ vimentin , ↑ Skp2 gegradation through the Ubiquitin-Proteasome-Dependent pathway	0, 10, 20, 40 and 80 µM	12
	U87 and U251	Inhibited angiogenesis,	↓ proliferation, migration and invasion of cancer cells , ↓ mRNA and protein levels of CD44, ↓ Snail, ↓ Vimentin ↓ ZEB1, ↓VEGF	0, 5, 10, 20 and 40 μM	15
	U251, U87MG, and A172	Induces apoptosis, pytoptosis, and protective autophagy	↓ viability and proliferation of GBM cells, induces G0/G1 Cell Cycle arrest, ↓ CCND1, ↓ CDK4, ↓ PCNA, ↓ cyclin-dependent kinase inhibitor p21, ↓ Bcl-2, ↑ BAX, ↑ cleaved PARP-1, ↑ nuclear DNA damage in GBM cells, ↑ formation of autophagic vesicles, ↑ MAP1LC3B-II, ↓ SQSTM1, ↑ AMPK activity, ↓ mTOR , ↓ P-AMPKα (Thr172)	0, 50, 100, 200, 400 μM	13
	A172	Induces apoptosis	↓ A172 cell migration and invasion, ↓ ADAM9 expression, ↑ p-ERK1/2, ↓ total expression of ERK1/2	0,5,10 and 25 μM	7
Nasopharyngeal	NPC-TW 039 and NPC-TW 076	Induces p53-independent S-phase arrest and apoptosis	↑ numbers of apoptotic bodies and ↑ condensed/fragmented nuclei, ↑ DNA fragmentation, ↓ PI3K-AKT Signaling Pathway, ↑ Cleavage of procaspase-3 and PARP, induced caspase-3 activation, ↑ apoptotic cells (sub-G1-phase population), ↓ p-AKT (Ser 473), ↓ PI3K, ↓ AKT, ↑ cleavage of pro-caspase-9, ↑ p21, ↑ BAX, ↑ BAD, ↑ BAK protein expression, ↓ BCL-2, ↓ BCL-xL protein levels	0–100 μM	45
Laryngeal	TU212 and M4e	Activating apoptosis and autophagy	↓ carcinoma cell viability, migration, invasion and proliferation, ↑ Bax, ↓ Bcl-2, ↑ caspase-3, ↑ caspase-9, ↑ PARP cleavage, ↑ LC3I, ↑ LC3II, ↑ Beclin 1, ↓ Raf, ↓ Ras. ↓ p-p38, ↓ PI3K/AKT, ↓ PI3K-Akt-mTOR signaling pathway, ↑ TSC1(inhibitor of mTOR activation), ↓ p- mTOR	0, 2.5, 5.0, 10.0, 20.0, 30.0 and 40.0 µM	42
Esophageal(galangin and berberine)	Eca9706,TE-1, and EC109	Induces apoptosis	↓ survival and growth cancer cells, cell cycle arrest at G2/M phase, ↑ ROS levels, ↓ Wnt3a, ↓ β-catenin, ↓ Cyclin B, ↓ Cyclin D, ↓ Cyclin E, ↓ CDK1, ↓ CDK2, ↓ CDK4, ↓ CDK6, ↓ transition of G2/M phase, ↑ P21, ↑ P27, ↑ P53, ↑ cleaved PARP, ↑ Caspase-3, ↓ Bcl-2, ↓ Mcl-, ↓ XIAP, ↑ Bax, ↑ PI3K, ↑ Rac, ↑ p-JAK2, ↑ p-STAT3	Galangin 0,2.5,5.0, 10.0,20.0,30.0,40.0 and 50 µM + Berberine 0,10,30,60, 90,120,160 and 200 µM	76
Retinoblastoma	Y-79, C-33A, and WERI-Rb-1	Induced apoptosis	↓ Human retinoblastoma cell proliferation and migration. ↑ PTEN, ↓ protein kinase B (Akt) phosphorylation, ↑ PIP3, ↑ PIP2, ↑ caspase-3, ↓ KI-67 positive levels, ↓ p-Akt (S473 and T308 sites), ↓ PIP2 , ↑ active Caspase-9, ↑ Caspase-3 expression levels	0, 5, 10, 20, 40, 80, and 100 uM	39
Osteosarcoma	MG-63 and U2-OS	Induced apoptosis	↓ cell proliferation, ↑ mRNA levels of Col I, ALP, OPN, and OC (osteoblastic differentiation markers), ↑ protein level of Runx2, ↑ TGF-b1 production, ↑ phosphorylation of Smad2 and Smad3	0, 25, 50 and 100 μM	90
	MG63 and U20S	Induces apoptosis	↓ proliferation, migration and invasion osteosarcoma cells, ↓ PI3K and Aktp (Thr308), ↓ cyclin D1, ↓ MMP 2/9, ↑ p27Kip1, ↑ caspase-3, ↑ caspase-8	0, 5, 10, 25, 50, 100, 200 and 300 µM	14
Fibrosarcoma	HT-1080	Inhibited metastasis	↓ MMP-9 secretion, ↓ MMP-9 mRNA, ↓ p-JNK, ↓ activation of NF-κB and AP-1, ↑ p-IκBα, ↓ IκBα	0,10, 30 and 100 µM	91
Breast	MCF-7	Induces apoptosis	↑ Bax and decreased the expression of Bcl-2, ↑ cleavage of caspase-9, ↑ caspase-8, ↑ caspase-3, ↑ Bid, ↑ Bad, ↓ p-PI3K, ↓ pAkt, ↓ cyclin D3, ↓ cyclin B1, ↓ CDK1, ↓ CDK2, ↓ CDK4, ↑ p21,↑ p27, ↑ p53	10, 20, 40, 80, and 160 µM	7
	MCF-7 and T47D	Induce apoptosis	↓ cancer cell lines viability, proliferation, ↓ BCl-2, ↑ ROS production, ↑ NADPH, ↑ caspase-3 activity, ↑ Caspase-9 activity, ↑ p-PERK, ↑ GRP78, ↑ CHOP, ↑ p-eIF2a, ↑ ATF4, ↑ p-AMPK, ↑ DR4, ↑ Caspase-9, ↑ Caspase-3 cleavage, ↑ Bax	Galangin 20 and 40 µM + TRAIL 100 and 200 ng/ml	43
Lung (galangin and cisplatin)	A549, DDP-resistant variant A549/DDP cells	Induce apoptosis	↓ cell proliferation, viability, migration and colony formation, ↓ p65 in nucleus, ↓ p-IκBα in whole cells, ↑ IκBα, ↓ p-STAT3, ↑ cleaved Caspase-3, ↑ PARP, ↓ Bcl-2, ↑ Bax, ↑ Bid	0, 2, 5 and 10 µM galangin + 2 µM DDP (cisplatin)	16
Colon	HCT-15 and HT-29	Induced apoptosis and DNA condensation	↓ cancer cell viability, ↑ nuclear rounding and shrinkage, ↓ caspase-3, ↓ caspase-9, ↑ release of apoptosis inducing factor from the mitochondria into the cytoplasm, alteration of mitochondria membrane potential and dysfunction	0, 5, 25, 50, 100 and 200 μM	10
Hepatocellular	MHCC97H	Promoted cell apoptosis	↓ H19, ↓ cell migration and invasion, ↓ S phase cells, mRNA of TP53- and p53-related genes (CDIP1, FOS, and CREB3L3) were significantly differentially expressed	0, 20, 50, 100 and 150 μM	11
	HepG2	Induces apoptosis	↓ HepG2 cell proliferation and viability, ↑cytoplasm shrinkage, disappearance of microvilli, ↑ shrinkage cytoplasm, distorted organelles and condensed chromatin ↓ mitochondrial membrane potential ↑ mitochondrial dysfunction, ↑ caspase-3 ↑ ROS production	Selenium nanoparticles with galangin (11 µM)	20
	HepG2, Hep3B and PLC/PRF/5	--	↓ proliferation of HCC cells, ↓ glucose absorption, ↓ lactate production, ↑ pyruvate kinase, ↓ Warburg effect, ↑ aerobic metabolism, ↓ glycolysis, ↓ glucose absorption, ↓ lactate production, ↑ glycolytic rate-limiting enzyme pyruvate kinase activity, ↓ Glut1, ↓ PKM2, ↓ LDHA, ↓ PDHK, ↑ HKII, ↑ PKM1, ↑ PDH, ↑ CS	0, 65, 130 and 260 µM	92
	HepG2	Induces autophagy	↑ binding of SIRT1-LC3, ↓ acetylation of endogenous LC3, ↑ LC3 II, ↑ Beclin1, ↑ ratio of LC3 II to LC3 I, ↓ p62, activating the TGF-β receptor/Smad pathway, ↑ AMP/TAN ratio, ↑ p53, ↑ glucose starvation	130 µM	70
	HepG2	Induced autophagy	↑ TGF-β receptor/Smad pathway activity, ↑ TGF-β receptor I (RI), ↑ TGF-β RII, ↑ Smad1, ↑ Smad2, ↑ Smad3, ↑ Smad4 levels, ↓ Smad6, ↓ Smad7, ↑ Beclin1, ↑ ATG16L, ↑ ATG12, ↑ ATG3 and ↑ LC3-II, ↑ number of cells with LC3 foci, ↑ TGF-β RI, ↑ TGF-β RII, ↑ phosphorylation of Smad1, Smad2 and Smad3, ↓ subG1 ratio	0, 37, 74 and 148 µM	93
	HepG2, Hep3B and PLC/PRF/5	Induce apoptosis	↓ proliferation and viability of carcinoma cells, ↑ endoplasmic reticulum stress, ↑ Ca2+ levels, ↑ GRP94, ↑ GRP78, ↑ CHOP, ↑ p38 MAPK, ↑ JNK, ↑ ERK	134.0, 87.3 and 79.8 µM	29
	HepG2, Hep3B, and PLC/PRF/5	Induced autophagy	↑ AMP/TAN, ↑p-AMPK, ↑ p- LKB1, ↓ p-AKT, ↓ p-mTOR, ↑ PARP, ↑ LC3-II, ↑ formation of autophagic vacuoles, ↑ cellular relative AMP level	0, 65,130 and 260 µM	30
Liver	Chang liver, AGS, Hep3B, and HepG2	Inhibited metastasis	↓ viability of cancer cells, ↓ TPA-induced enzyme activity, ↓ MMP-2 and MMP-9, ↓PKCα, PKCδ, ↓ p-ERK1/2, phospho-IκBα, ↓c-Fos, ↓ c-Jun, ↓ NF-κB	0, 1, 2.5, 5, 10, 15, 20, 25, and 30 μM	62
Cholangiocarcinoma	HCCC9810 and CCA cell line TFK-1	Induces cell apoptosis	↓ proliferation, migration, and invasion of cancer cells, ↓ microRNA-21 (miR-21) expression, ↓ p-AKT, ↓ MMP9, ↓ Vimentin, ↑ PTEN, ↑ cleaved caspase 3 protein expression, ↑ ratio of Bax to Bcl-2	0, 50, 100, 150, or 200 μM	40
Gastric	MGC 803	Promoted apoptosis	↓ cancer cell proliferation, ↓ Ki67, ↓ PCNA, ↓ Bcl-2, ↑ cleaved caspase- 3, ↑ cleaved PARP, inactivated JAK2/STAT3 pathway, ↑ ROS, ↓ Nrf2, ↓ NQO-1, ↑ HO-1, ↓ caspase-3, ↓ p-JAK2, ↓ p-STAT3	0, 5, 10, 20, 40, 80, 120, 160 and 200 μM	9
	SNU-484	Induces apoptosis	↓ viability of SNU-484 cells, ↑ chromatin condensation and DNA damage, ↑ Bax, ↓ Bcl-2, ↓ Bcl-xl, ↑ caspase-3, -9, and PARP, protein ↓ levels of glutathione S-transferase P, ↓ peroxiredoxin 5, ↓ cytochrome c oxidase subunit 5 A (mitochondrial), ↓ Bfl-1 in complex with Noxa Bh3 peptide, ↑ carboxylterminal hydrolase isozyme L1,↑ nucleoside diphosphate kinase A, ↑ eukaryotic translation initiation factor 5 A-1, ↑ galectin-1	0, 25, 50,7 5, 100, 125, 150, 175 and 200 μM	94
Pancreatic	PANC-1	Induced apoptosis	↓ cell proliferation viability, ↓p-Thr-179 site at Smad3 linker region, ↓ p-CDK4, ↑ p21 (TGF-b1-induced tumor suppressor), ↑ PARP, ↑ caspase-3	0, 25, 50 and 100 μM	95
Renal	A498	Induction of Mitochondrial mediated apoptosis	↑ protein expression of Bax and Cyt-c ↓ Bcl-2, ↓ motility, Invasion and migration of the A498 cells, ↓ p-PI3K, ↓ pAKT, ↓ p-mTOR proteins, ↓ PI3K/AKT/mTOR signaling pathway,	0, 10, 20 and 40 μM	41
	Caki, ACHN and A498	Induce apoptosis	↑ sub-G1 population, ↑ PARP cleavage, caused chromatin damaged in the nuclei, ↓ Bcl-2 ↓ NF-κB activation, ↓ cFLIP, ↓ Mcl-1, ↓ survivin expression (at the post-translational levels), ↑ proteasome activity	0. 50. 100, 50. 200 and 250 µM + TRAIL 100, 200, 300 and 400 ng/ml	44
Prostate	PC3M and DU145,	Induced apoptosis	↓ cell proliferation viability, ↓p-Thr-179 site at Smad3 linker region, ↓ p-CDK4, ↑ p21 (TGF-b1-induced tumor suppressor), ↑ PARP, ↑ caspase-3	0, 25,50, and 100 μM	95
Cervical	HeLa	Induction of apoptosis	↓ proliferation and migration of HeLa cells, ↑ ROS production, ↓ cytotoxic metabolite methy glyoxal, ↓ Nrf-2 (a trascription factor), ↓ glyoxalase-1, ↑ oxidative and carbonyl stress, ↑ total carbonyl content (an indicator of oxidation damage)	0, 25, 50,100 and 150 μM	38
Ovarian	A2780/CP70 and OVCAR-3	Induces apoptosis	↓ proliferation of ovarian cancer cells, ↑ cleaved caspase-3, caspase-7 and PARP-1, ↓ procaspase-3, ↓ procaspase-7, ↑ DR5, ↑ cleaved caspase-8 and ↓ procaspase-8 , ↑ Bax protein, ↓ Bcl-2, ↓ procaspase-9, ↑ p53, ↑ p21 protein expressions , ↓ p-Akt, ↓ p-p70S6K, ↓ cmyc protein levels	0,10, 20, 40, 80 and 160 µM	8
	OVCAR-3 and A2780/CP70	Anti-angiogenic	↓ VEGF, ↓ p-Akt,↓ p-70S6K, ↓ HIF-1α proteins, ↓ secretion of VEGF by the Akt/p70S6K/ HIF-1α pathway,	0, 10, 20, 40, 80 and 160 µM	58