Preventive and Therapeutic Roles of Berberine in Gastrointestinal Cancers

Table 1

Suppressive effect of BBR on GI cancer.

Drugs	Type of regulation	Mechanism	Cell lines/animal model	References
Coptidis rhizome (CR)	Anticachectic	IL-6↓	Esophageal cancer model	Iizuka et al. [14]
BBR	Antiproliferation; Proapoptosis	G2/M arrest↑ P21↑; Akt/mTOR↓ p-AMPK↑	Human esophageal squamous carcinoma cell line KYSE-70 cells	Jiang et al. [11]
BBR	Antiproliferation; Anti-invasion	Cxc chemokine receptor 4 and Cxc chemokine receptor 7↓	Esophageal cancer cells	Mishan et al. [15]
BBR and galangin	Antiproliferation; Proapoptosis	G2/M arrest↑; ROS↑Wnt3a ↓β-catenin↓	Esophageal cancer cells/model	Ren et al. [16]
BBR	Proradiosensitivity	VEGF and HIF-1α↓	Esophageal squamous cell carcinoma	Yang et al. [17]
BBR	Proradiosensitivity	RAD51↓	Esophageal cancer cells	Liu et al. [18]
BBR	Antiproliferation; Antimigration	ROS↑NF-κB p65↓MMP-1 -2, and -9↓	GC cells	Lin et al. [22]
BBR	Proapoptosis	Caspase-3↑ cleaved poly ADP-ribose polymerase↑; The damage of mitochondrial membrane potential; Akt/mTOR/p70S6/S6↓	GC cells	Yi et al. [24]
BBR	Antiproliferation	STAT3↓survivin↓	Gastric adenocarcinoma cells	Pandey et al. [28]
BBR and 5-FU	Antichemotherapy resistance	STAT3↓survivin↓	Gastric adenocarcinoma cells	Pandey et al. [28]
BBR	Antiproliferation; Antimigration	COX-2/PGE2↓; p-JAK2↓p-STAT3↓MMP-2/-9↓	CRC cells	Liu et al. [29]
BBR	Antiproliferation	G2/M arrest↑ cyclin B1↓cdc2↓cdc25c↓	Human colorectal adenocarcinoma cells	Cai et al. [30]
BBR	Antiproliferation; Proapoptosis	AMPK↑mTOR↓NF-κB↓cyclin D1↓survivin↓p-p53↑caspase-3↑	Colorectal carcinogenesis mouse model; CRC cells	Li et al. [31]
BBR	Antiproliferation; Proapoptosis	ATF3 ↑ NAG-1↑	CRC cells	Piyanuch et al. [32]
BBR	Antiproliferation; Antitumorigenesis	TNF-α↓ IL-6↓in macrophages; EGFR-ERK signaling↓	Colitis-associated colorectal cancer (CACRC) mice model and RAW 264.7 macrophages and colon cancer HCT116 cells	Li et al. [33]
BBR	Proautophagy	GRP78↑	Colon cancer cells	La et al. [34]
BBR	Antiglucose uptake; Antiglucose metabolic	GLUT1↓LDHA↓HK2↓ HIF-1α protein↓; mTOR phosphorylation↓	Colon cancer cells	Mao et al. [35]
BBR	Anti-intestinal polyps	Wnt↓cyclin D1↓ c-Myc↓	ApcMin/+ mice	Zhang et al. [36]
BBR	Anti-intestinal polyps	β-Catenin signaling pathway↓	Nude mice	Ruan et al. [37]
BBR	Anticancer stem cells; Antimetastasis	Cancer stem cells↓ SOX2↓, POU5F1↓, NANOG↓	Pancreatic cancer cells	Park et al. [38]
BBR	Antiproliferation; Proapoptosis	G1/S arrest↑; ROS↑	Pancreatic cancer cells	Park et al. [39]
BBR	Antiproliferation; Proapoptosis	Caspase-3↑caspase-7↑; BRCA1-mediated DNA damage↑; G1/S arrest ↑G2/M arrest↑; P53 signaling pathways ↑	Pancreatic cancer cells	Pinto-Garcia et al. [40]
BBR	Antiproliferation	G1/S arrest ↑	Hamster cholangiocarcinoma (CCA) cells	Puthdee et al. [41]
BBR	Antiproliferation	G0/G1 arrest ↑CDKIs p21Cip1↑; p27Kip1↑	HCC cells	Li et al. [42]
BBR	Promitochondrial impairment; Proapoptosis	PHLPP2-Akt-MST1 kinase signaling pathway	HCC cells	Saxena et al. [43]
BBR and sorafenib	Antiproliferation; Proapoptosis	ADP-ribose polymerase↑ caspase-3↑ BCL-2↓VEGF↓	HCC cells	Huang et al. [44]
BBR and HMQ1611 (BCH)	Antiproliferation; Antimigration	G1 phase arrest ↑ Wnt/β-catenin signaling pathway↓	HCC cells	Dai et al. [45]
BBR	Antiproliferation; Proapoptosis	347 miRNAs ↑; 93 miRNAs↓; 78 novel miRNAs were identified	GC cells	Yang et al. [46]
BBR	Cisplatin sensitivity↑; Proapoptosis	miRNA-203↑Bcl-w↓	GC cells	You et al. [49]
BBR	Antiproliferation; Antitumorigenesis	DNMT1↑, DNMT3A↑, DNMT3B↑ and miRNA-152↑, miRNA-429↑, miRNA-29a↑	Colon cancer tissues	Huang et al. [50]
BBR	Proapoptosis	miRNA-429↓	Colorectal tissue	Liu et al. [52]
BBR and NVP-AUY922	Antiproliferation	CDK4↓miR-296↑Pin1-β-catenin-cyclin D1 signaling pathway↓	Human colon adenocarcinoma cells	Su et al. [55]
coptisine (COP)	Antiproliferation; Antimigration; Proapoptosis	miR-122↑	HCC cells hepatocellular carcinoma nude mice	Chai et al. [56]
BBR	Antiproliferation; Proapoptosis	lncRNA CASC2↑BCL2↓	CRC cells	Dai et al. [60]
BBR	Antidevelopment of intestinal cancer modified gut microbiota’s structure	Akkermansia↓; Short chain fat acid; (SCFA)-producing bacteria↑	Multiple intestinal neoplasia mice	Wang et al. [64]
BBR	Antigenesis of CRC induced by Fusobacterium nucleatum	Fusobacterium nucleatum↓ IL-21/22/31↓CD40L ↓p-STAT3↓, p-STAT5 ↓ p-ERK1/2↓	Multiple intestinal neoplasia mice	Yu et al. [66]