Table 1.

The antitumor activities and mechanisms of five bufadienolides.

Compounds	Subjects (cells/animals)	Concentration	Safe dose for animals	Research Mechanisms	Main mechanisms	Tumor Types	References
Telocinobufagin	4T1 cells, breast cancer cells, HCT116 cells, SW480 cells, and BALB/c mice splenocytes	0.1~10 μM or 1, 5, 25 and 125 mg/L	10 or 20 µg/mouse	PI3K/Akt/ERK/Snail signaling pathway PI3K/Akt pathway MMP-2, MMP-9 synthetic signaling pathway Bax pathway activation Th1 cytokine regulatory pathway	Apoptosis, necrosis, inhibition of proliferation and migration, activation of immune cells	Breast cancer, Colorectal cancer, Potential treatment	(59, 60)
Bufotalin	Hep 3B cells, Hep G2 cells, R-HepG2 cells, U2OS cells, SaOs-2 cells, MG-63 cells, HeLa cells, A375 cells, ESCC cell lines, and BGC-823 cells	0.01~10 μM	0.5 mg/kg	caspases pathway Akt-mediated signal pathway endoplasmic reticulum stress Bid- and STAT1-dependent pathways The mitochondrial apoptotic pathway p53 signaling pathway caspase-3 apoptosis pathway	Apoptosis, cell necrosis, inhibition of proliferation and migration, cell cycle arrest, inhibition of DNA repair, ER stress	Hepatocellular carcinoma, Malignant osteoblastoma, Cervical cancer, Cutaneous malignant melanoma, ESCC, and Gastric cancer	(61–67)
Bufalin	T24 cells, SK-N-BE cells, SH-SY5Y cells, U251 cells, U87MG cells, LN-229 cells, HepG2 cells, BxPc3 cells, and Sw1990 cells	1~300 nM	5 mg/kg	caspase pathway AKT pathway EPK pathway electron transport chain pathway endoplasmic reticulum stress Fas- and mitochondria-mediated pathways TBK1 activation pathway cellular gene transcriptional	Apoptosis, cell necrosis, inhibition of proliferation and migration, cell cycle arrest, enhancement of cell sensitivity, inhibition of metastasis, oxidative stress, ER stress	Bladder cancer, drug-resistant bladder cancer, Neuroblastoma, Glioblastoma, Hepatocellular carcinoma, and Pancreatic cancer	(68–80)
Cinobufotalin	A549 cells, H460 cells, HTB-58 cells, HONE1-EBV cells, 5–8F cells, HepG2 cells, LM3 cells, SMMC7721 cells, KYN-2 cells, Huh-7 cells, SNU-739 cells, and Male SD rats	0.025~10 μM or 20, 200 and 2000 ng/mL	4 mg/kg	mPTP opening pathway EMT signals Pathway MYH9 expression Pathway targeting lipogenesis Induces cells to produce ceramide mitochondrial pathway Regulation of P-glycoprotein	Apoptosis, cell necrosis, inhibition of proliferation and migration, reduction of ATP synthesis, enhancement of cell sensitivity, inhibition of metastasis and invasion	Lung cancer, Nasopharyngeal Carcinoma, and Hepatocellular carcinoma	(81–86)
Cinobufagin	HepG2 cells, MG-63 cells, 143B cells, U2OS cells, SaOS-2 cells, HCT116, RKO cells, SW480 cells, HK-1 cells, and SGC-7901 cells	0.001~1000 µM	1.0 mg/kg	Fas- and mitochondria-mediated pathways Notch signaling pathway IL-6-OPN-STAT3 pathway GSK-3/NF-κB pathway STAT3 pathway Akt/mTORC1/HIF-1α pathway mitochondrial pathway	Apoptosis, cell necrosis, inhibition of proliferation and migration, cell cycle arrest, inhibition of angiogenesis, inhibition of metastasis and invasion, inhibition of autophagy	Hepatocellular carcinoma, Osteosarcoma, Colorectal cancer, Nasopharyngeal Carcinoma, and Gastric cancer	(55, 69, 87–92)