Research progress in the anti-cancer activity and related mechanisms of arenobufagin

doi:10.3969/j.issn.1674-8115.2024.03.012

Abstract

Abstract:

Toad venom is an active extract of toad, which is processed by distilling or drying at high temperature the venom secreted from the skin glands and ear-side glands of Toad Chinensis. As a natural product that has been used to treat diseases in China for thousands of years, toad venom has many pharmacological effects such as heart strengthening, analgesia, anti-myocardial ischemia, anti-endotoxin shock, and anti-cancer. Arenobufagin (ARE) is one of the main chemical components of toad venom, and its anti-cancer mechanism has been increasingly clarified in the past decade. ARE can play an anti-cancer role through a variety of ways, such as inducing apoptosis and/or autophagy of cancer cells, necrosis, and cell cycle arrest, inhibiting cancer cell migration and invasion, and inhibiting angiogenesis. The current research on ARE mainly focuses on the selective toxicity of cancer cells and the molecular mechanism of anti-cancer, mostly at the cellular and animal levels. Due to the large toxic and side effects of ARE, unclear targets and unclear pharmacokinetic characteristics, ARE has not yet entered the clinical application in Western medicine. This article summarizes relevant research results on the anti-cancer activity and molecular mechanism of ARE, and its combination with other anti-cancer drugs in order to provide a new direction for improving the anti-cancer mechanism of ARE.

Key words: arenobufagin (ARE), toad venom, anti-cancer, molecular mechanism

CLC Number:

R453.9

BAI Wenhui, SHEN Shukun, WU Yingli. Research progress in the anti-cancer activity and related mechanisms of arenobufagin[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(3): 385-392.

Figures/Tables 2

TrendMD

References 35

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Type of tumor	Type of cell	IC₅₀
Pancreatic cancer	Panc-1	10 nmol/L^[11]
	AsPC-1	1 nmol/L^[11]
	SW 1990	9.9 nmol/L^[12]
	BxPC-3	48.72 nmol/L^[5]
Lung cancer	A549	10 nmol/L^[13-14]
Breast cancer	MCF 7	485 nmol/L^[10,15]
Esophageal carcinoma	Eca-109	0.8 μmol/L^[8]
Esophageal carcinoma	TE-11	3.6 μmol/L^[8]
Glioma	U-87 MG	10.3 nmol/L^[9]
Cervical cancer	HELA	23 nmol/L^[10]
Colon cancer	HT-29	25 nmol/L^[10]

Type of tumor	Type of cell	IC₅₀
Pancreatic cancer	Panc-1	10 nmol/L^[11]
	AsPC-1	1 nmol/L^[11]
	SW 1990	9.9 nmol/L^[12]
	BxPC-3	48.72 nmol/L^[5]
Lung cancer	A549	10 nmol/L^[13-14]
Breast cancer	MCF 7	485 nmol/L^[10,15]
Esophageal carcinoma	Eca-109	0.8 μmol/L^[8]
Esophageal carcinoma	TE-11	3.6 μmol/L^[8]
Glioma	U-87 MG	10.3 nmol/L^[9]
Cervical cancer	HELA	23 nmol/L^[10]
Colon cancer	HT-29	25 nmol/L^[10]

Type of tumor	Type of cell	Up-regulation	Down-regulation
Pancreatic cancer, lung cancer, breast cancer, esophageal squamous cell carcinoma, osteosarcoma^{[6, 11, 16]}	BxPC-3, SW 1900, A549, NCI-H460, MCF 7, Eca-109	Cleaved CASPASE 9
Pancreatic cancer, lung cancer^{[11, 16]}	BxPC-3, SW 1900, A549, NCI-H460	Cleaved CASPASE 3
Pancreatic cancer, lung cancer, liver cancer, breast cancer^{[6, 11]}	BxPC-3, SW 1900, A549, NCI-H460, HepG2/ADM, MCF 7	Cleaved PARP
Esophageal squamous cell carcinoma^[8]	Eca-109	Cleaved CASPASE 8
Breast cancer^[17]	MCF 7, MDA-MB-468	NOXA
Breast cancer, esophageal squamous cell carcinoma, pancreatic cancer^{[5, 8, 15-16]}	MCF 7, MDA-MB-468, Eca-109, SW 1990, BxPC-3	P53
Liver cancer, breast cancer, lung cancer, acute leukemia^{[6, 13, 15, 18]}	HepG2/ADM, MCF 7, A549, Jurkat, MV-4-11, PC-9	BAX
Breast cancer^[15]	MCF 7	P-JNK
Acute leukemia^[18]	Jurkat, MV-4-11	AIF
Liver cancer^[6]	HepG2/ADM	LC3Ⅱ
Breast cancer^[13]	HELA	ROS
Pancreatic cancer^[5]	SW 1990, BxPC-3	SMAD3
Pancreatic cancer, breast cancer, lung cancer^{[11, 15, 19-20]}	Panc-1, AsPC-1, PC-9		P-ERK
Pancreatic cancer, breast cancer^{[5, 6, 11, 21]}	Panc-1, AsPC-1		P-AKT
Breast cancer^[16]	MCF 7, MDA-MB-48		MCL-1
Lung cancer^[19]	PC-9		P-MEK
Liver cancer, lung cancer^{[13, 19]}	HepG2/ADM, A549, PC-9		BCL-2
Pancreatic cancer^[5-6]	SW 1990, BxPC-3		PI3K
Lung cancer^{[6, 19]}	PC-9		C-RAF
Pancreatic cancer^[5-6]	SW 1990, BxPC-3		mTOR
Liver cancer^[14]	HepG2		STAT3
Acute leukemia^[18]	Jurkat, MV-4-11		XIAP
Liver cancer^[6]	HepG2/ADM		LC3Ⅰ
Lung cancer^[13]	A549		SOD
Lung cancer^[20]	A549		GSH
Pancreatic cancer^[5]	SW 1990, BxPC-3		AMPK
Pancreatic cancer^[5]	SW 1990, BxPC-3		P62

Type of tumor	Type of cell	Up-regulation	Down-regulation
Pancreatic cancer, lung cancer, breast cancer, esophageal squamous cell carcinoma, osteosarcoma^{[6, 11, 16]}	BxPC-3, SW 1900, A549, NCI-H460, MCF 7, Eca-109	Cleaved CASPASE 9
Pancreatic cancer, lung cancer^{[11, 16]}	BxPC-3, SW 1900, A549, NCI-H460	Cleaved CASPASE 3
Pancreatic cancer, lung cancer, liver cancer, breast cancer^{[6, 11]}	BxPC-3, SW 1900, A549, NCI-H460, HepG2/ADM, MCF 7	Cleaved PARP
Esophageal squamous cell carcinoma^[8]	Eca-109	Cleaved CASPASE 8
Breast cancer^[17]	MCF 7, MDA-MB-468	NOXA
Breast cancer, esophageal squamous cell carcinoma, pancreatic cancer^{[5, 8, 15-16]}	MCF 7, MDA-MB-468, Eca-109, SW 1990, BxPC-3	P53
Liver cancer, breast cancer, lung cancer, acute leukemia^{[6, 13, 15, 18]}	HepG2/ADM, MCF 7, A549, Jurkat, MV-4-11, PC-9	BAX
Breast cancer^[15]	MCF 7	P-JNK
Acute leukemia^[18]	Jurkat, MV-4-11	AIF
Liver cancer^[6]	HepG2/ADM	LC3Ⅱ
Breast cancer^[13]	HELA	ROS
Pancreatic cancer^[5]	SW 1990, BxPC-3	SMAD3
Pancreatic cancer, breast cancer, lung cancer^{[11, 15, 19-20]}	Panc-1, AsPC-1, PC-9		P-ERK
Pancreatic cancer, breast cancer^{[5, 6, 11, 21]}	Panc-1, AsPC-1		P-AKT
Breast cancer^[16]	MCF 7, MDA-MB-48		MCL-1
Lung cancer^[19]	PC-9		P-MEK
Liver cancer, lung cancer^{[13, 19]}	HepG2/ADM, A549, PC-9		BCL-2
Pancreatic cancer^[5-6]	SW 1990, BxPC-3		PI3K
Lung cancer^{[6, 19]}	PC-9		C-RAF
Pancreatic cancer^[5-6]	SW 1990, BxPC-3		mTOR
Liver cancer^[14]	HepG2		STAT3
Acute leukemia^[18]	Jurkat, MV-4-11		XIAP
Liver cancer^[6]	HepG2/ADM		LC3Ⅰ
Lung cancer^[13]	A549		SOD
Lung cancer^[20]	A549		GSH
Pancreatic cancer^[5]	SW 1990, BxPC-3		AMPK
Pancreatic cancer^[5]	SW 1990, BxPC-3		P62

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