Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway

Abstract

Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (ΔΨm) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of ΔΨm, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy.

Berberine: Pathways to protect neurons

“…In another research by Eom, Kim, So, Park, and Kim () demonstrated that BBR induces apoptosis by mediating endoplasmic reticulum stress and mitochondrial dysfunction in human glioblastoma T98G cells. This contrary side of BBR is applied in its therapeutic effect in cancer by promoting ROS generation and mitochondrial‐related apoptotic pathway (Xie et al, ). As a consequence, these evidences may prove that BBR has dual effect in the treatment of nervous diseases and its dose‐dependent manner may be one of the reasons.…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Several mechanisms have been identified for the anti-proliferative effects of berberine, including down-regulation of cyclins A, D, cyclin-dependent kinase (CDK) 1, CDK4, MMP-2 and janus kinase 2 (Jak2)/vascular endothelial growth factor (VEGF)/NF-κB/activator protein 1 (AP-1) pathway, and induction of autophagic cell death via mTOR signaling pathway [149,155,156]. Berberine also induces mitochondrial-mediated apoptosis through the loss of mitochondrial membrane potential, cytochrome c release, caspase and PARP activation, up-regulation of pro-apoptotic Bcl-2 family proteins, and down-regulation of antiapoptotic Bcl-2 family proteins [150,[157][158][159]. It can also activate apoptosis-inducing factor to induce ROSmediated cell death in pancreatic, breast, and colon cancers [158,160,161].…”

Berberine and barberry (Berberis vulgaris): A clinical review

“…Berberine induces reactive oxygen species (ROS) production and activates mitochondria‐dependent apoptosis in prostate cancer cells (Meeran, Katiyar, & Katiyar, ). It also induced ROS‐mediated cell death and apoptosis in pancreatic, breast, and colon cancer through activation of apoptosis‐inducing factor (Park, Sung, Kim, & Chung, ; Wang et al, ; Xie et al, ).…”