Berberine induces mitochondrial‑mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI‑H2452 cells

Abstract

Increasing evidence shows that berberine has antitumor effects against a number of tumor cells. In the present study, we evaluated the effect of berberine on the proliferation of the human malignant pleural mesothelioma (MPM) cell line NCI-H2452, and explored the therapeutic potential and underlying mechanisms of this agent. Our results showed that berberine inhibited the proliferation of NCI-H2452 cells in a dose-and time-dependent manner and could induce apoptosis, possibly through a caspase-9-dependent intrinsic mitochondrial pathway. In addition, autophagy was induced by berberine, which was characterized by the accumulation of LC3-II and decreased p62 expression. We used inhibitors of apoptosis and autophagy, and an inducer of autophagy, to evaluate the significance of autophagy in berberine-induced cell death. The results demonstrated that apoptosis is the primary route through which berberine induces NCI-H2452 cell death. Berberine-induced autophagy may be an adaptive response to antitumor agents and have a protective role in MPM cells. Inhibition of autophagy enhanced berberine-induced apoptosis. Therefore, inhibition of autophagy may be an effective treatment strategy in the management of MPM. In conclusion, berberine is a potent antitumor agent for treating MPM, and it induces mitochondrial-mediated apoptosis and protective autophagy in human NCI-H2452 MPM cells.

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

“…In addition, berberine can induce autophagic cancer cell death through increased GRP78 levels and enhancing the binding ability of GRP78 to VPS34 in human colorectal cancer HCT-116 cells [148], whilst it induces autophagy through inhibiting AMPK/mTOR/UNC-51-like kinase 1 (ULK-1) pathway in human glioma U251 and U87 cells [149]. In contrast, berberine induces protective autophagy in human malignant pleural mesothelioma NCI-H2452 cells, and inhibition of autophagy promotes berberine-induced apoptosis [150]. Therefore, autophagy plays a dual role in berberine-induced apoptosis.…”

“…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: A novel therapeutic strategy for cancer

“…These findings suggest that induced apoptosis by BBR can occur in the NCI-H2452 human Malignant Pleural Mesothelioma (MPM) cells through the signaling of cytochrome c/caspase-9 and -3. 87 As demonstrated by the recent experiments, BBR exhibits cytotoxicity and induces apoptosis in human leukemia cells. For instance, an investigation revealed that in HL-60 and WEHI-3 Acute Myeloid Leukemia (AML) cell line, the apoptosis was induced by the activation of caspase-3 and depolarization of mitochondrial membrane by BBR treatment.…”

Combination of Berberine and Matrine Affects Apoptosis and Cellcycle in Human Cervical Cancer Cells

“…The results of the analysis of berberine-and matrine-induced apoptosis are shown in Figures 2 and 3. Co-incubation with berberine and matrine significantly increased apoptosis in HeLa and SiHa cells with apparent synergism (32)(33). The apoptosis rates (early plus late apoptosis) of HeLa and SiHa cells in the normal control samples were 2.0 ± 0.4% and 1.9 ± 0.4%, and those of berberine-treated HeLa and SiHa cells were 16.2 ± 1.5% and 18.9 ± 1.4%, respectively.…”