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Bufalin Induces Apoptosis via Mitochondrial ROS-mediated caspase-3 Activation in HCT-116 and SW620 Human Colon Cancer Cells

Bufalin Induces Apoptosis via Mitochondrial ROS-mediated caspase-3 Activation in HCT-116 and SW620 Human Colon Cancer Cells

Di Wu, Wen-Yi Zhou, Xiao-Tong Lin, Lei Fang, Chuan-Ming Xie

Drug Chem Toxicol. 2019 Jul;42(4):444-450.

PMID: 30777466

Abstract:

Objective:
Bufalin has been reported to kill various types of cancer including human colorectal cancer. Our previous study demonstrated that bufalin induced cell death via autophagy in HT-29 and Caco-2 colon cancer cells, but the action of bufalin remains unclear. This study was conducted to investigate the role of bufalin in other colon cancer HCT-116 and SW620 cells as well as its potential mechanism.
Methods:
The effect of bufalin in HCT-116 and SW620 colon cancer cells was detected by assessing cell viability and cell death. Apoptotic cells were analyzed by Western blot and trypan blue dye exclusion assay. Mitochondrial ROS production was analyzed by flow cytometry after DCFDA and DHR-123 staining. The potential mechanism was investigated via pharmacological inhibitors.
Results:
Bufalin had high potency against HCT-116 and SW620 cells with IC50 values of 12.823 ± 1.792 nM and 26.303 ± 2.498 nM in HCT-116 and SW620 cells, respectively. Bufalin decreased cell viability, increased cell death as well as caspase-3 downstream target (cleaved PARP) accumulation, and these actions were significantly blocked by pan-caspase inhibitor zVAD-FMK. Mechanistically, ROS production, but neither the NAD(P)H oxidase, AMPK, ERK nor p38, is responsible for bufalin-induced apoptotic cell death. Moreover, bufalin-induced ROS generation is derived from mitochondria.
Conclusion:
Bufalin significantly induces apoptosis in HCT-116 and SW620 colon cancer cells via mitochondrial ROS-mediated caspase-3 activation. We believe that our novel findings will greatly alter our current understanding on the anti-cancer mechanism of bufalin in colon cancer cells and will pave the way for further exploiting the clinical application.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP465214	Bufalin		465-21-4	Price

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