Open Access

ARTICLE

Mechanisms involved in the cytotoxic effects of berberine on human colon cancer HCT-8 cells

by LI-NA XU, BI-NAN LU, MING-MING HU, YOU-WEI XU, XU HAN, YAN QI, JIN-YONG PENG

1. College of Pharmacy, Dalian Medical University, 9 Western Lvshun South Road, Dalian 116044, China.
2. Institute of Chinese Minority Traditional Medicine, Minzu University of China, 27 Zhongguancun South Avenue, Hadian district, Beijing 100081, China.
3. Research Institute of Integrated Traditional and Western Medicine of Dalian Medical University, Dalian 116011, China.

*Address correspondence to: Jinyong Peng. E-mail:

BIOCELL 2012, 36(3), 113-120. https://doi.org/10.32604/biocell.2012.36.113

Abstract

Berberine, a constituent of some traditional Chinese medicinal plants, has been reported to have cytotoxicity effects on different human cancer cell lines. There is no available information about the effects and mechanism of action of berberine on human colon cancer cell line HCT-8. In this paper, the cytotoxicity of berberine on HCT-8 cancer cells was investigated by MTT assay, fluorescence microscopy and flow cytometry analysis. Our data revealed that berberine could significantly inhibit the growth of HCT-8 cells in a dose- and time-dependent manner. Morphology of apoptotic cells was studied with acridine orange/ ethidium bromide staining. The concentrations of lactate dehydrogenase and both acid and alkaline phosphatases were significantly increased in cell supernatants after berberine treatment, suggesting cell death. Furthermore, flow cytometry analysis showed that berberine could arrest HCT-8 cells at S phase in a timedependent manner. To further investigate the apoptotic molecular mechanism, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were used. The up-regulated mRNA and/or protein expressions of Fas, FasL, TNF-α, caspase-3 and down-regulation of pro-caspase-3 suggest that the death receptor pathway may be involved in the apoptotic pathway induced by berberine. Decrease of Bcl-2 and increase of Bax in mRNA and/or protein expressions showed that the Bcl-2 family proteins were involved in berberine-induced apoptosis. We also found that berberine-induced apoptosis was associated with an upregulated expressions of p53 and prohibitin (PHB), and decreased vimentin expression. These results suggest that berberine can suppress cell growth and reduce cell survival by arresting the cell-cycle and by inducing apoptosis of HCT-8 cells.

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