Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells

Abstract

Berberine, a main component of Coptidis Rhizoma, is a plant alkaloid with a long history of medicinal use in Chinese medicine. Berberine has indicated significant antimicrobial activity against a variety of organisms including bacteria, viruses, fungi. The mechanism by which berberine initiates apoptosis remains poorly understood. In the present study, we demonstrated that berberine exhibited significant cytotoxicity in hepatoma HepG2 cells but is ineffective in Chang liver cells. Herein we investigated cytotoxicity mechanism of berberine in HepG2 cells. The results showed that HepG2 cells underwent internucleosomal DNA fragmentation after 24-h treatment with berberine (50 microM). Moreover, berberine induced the activation of caspase-8 and -3, and caused the cleavage of poly ADP-ribose polymerase (PARP) and the cytochrome c release, whereas the expression of Bid and anti-apoptosis factor Bcl-XL were decreased markedly. The loss of mitochondrial membrane potential (Delta psim) at 24 h and activation of Fas at 12 h were also seen in the berberine-treated HepG2 cells. These findings supported the fact that the inhibitors of caspases, DEVD-FMK, IETD-FMK and VAD-FMK, prevented apoptosis and restored the expression of Bcl-XL, Bcl-2 and Bid. These results indicated that the potential of anti-hepatoma activity of berberine may be mediated through a caspases-mitochondria-dependent pathway.

Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line

“…In addition, mitochondrial participation in berberine-induced apoptosis has been demonstrated in a number of studies [2,6,11,38]. Mitochondrially-relevant eVects of berberine exposure include changes in Bcl-2/Bax ratios, reactive oxygen species production, and a reduction in mitochondrial membrane potential [6,11]. In this report, we demonstrate that berberine induces mitochondrial fragmentation and diminishes polarization in K1735-M2 and WM793 melanoma cells.…”

“…Previous studies in fact have shown that berberine inhibits NADH dehydrogenase and respiratory activity [23,37]. In addition, mitochondrial participation in berberine-induced apoptosis has been demonstrated in a number of studies [2,6,11,38]. Mitochondrially-relevant eVects of berberine exposure include changes in Bcl-2/Bax ratios, reactive oxygen species production, and a reduction in mitochondrial membrane potential [6,11].…”

“…Berberine has been reported to induce apoptosis through a mitochondrial pathway that includes upregulation of p53, alterations in Bcl-2/Bax ratios, a decrease in mitochondrial membrane potential, release of cytochrome c, and activation of caspases [2,[6][7][8][9][10][11][12]. This is of particular interest in light of studies demonstrating a mitochondrial localization of berberine, raising the possibility that apoptosis results from mitochondrial damage induced by berberine.…”

Berberine in combination with cisplatin suppresses breast cancer cell growth through induction of DNA breaks and caspase-3-dependent apoptosis

“…BBR has been reported to possess a wide variety of pharmacological activities as an anti-microbial and anti-inflammatory agent (12)(13)(14)(15). Currently, the anticancer activities of BBR have been reported in a range of cancers including hepatoma, prostate cancer, glioblastoma, ovarian cancer, leukemia and breast cancer (16)(17)(18)(19)(20)(21)(22)(23)(24). BBR achieves its antitumor effect through inhibition of cell proliferation and induction of tumor cell apoptosis although the underlying molecular mechanisms of BBR involved in the inhibition of cancer cell growth have not been fully elucidated (25)(26)(27)(28)(29).…”

Systematic analysis of berberine-induced signaling pathway between miRNA clusters and mRNAs and identification of mir-99a∼125b cluster function by seed-targeting inhibitors in multiple myeloma cells

“…[1][2][3] Recent studies indicated that BBR down-regulates both the mRNA and protein levels of IL-6, which is a key factor in the proliferation of multiple myeloma (MM) cells. 4,5 Thus, it is possible that BBR may be effective in suppressing MM cells.…”