Matrine induces caspase-independent program cell death in hepatocellular carcinoma through bid-mediated nuclear translocation of apoptosis inducing factor

Abstract

Matrine, a clinical drug in China, has been used to treat viral hepatitis, cardiac arrhythmia and skin inflammations. Matrine also exhibits chemotherapeutic potential through its ability to trigger cancer cell death. However, the mechanisms involved are still largely unknown. The objective of this study was to investigate the major determinant for the cell death induced by matrine in human hepatocellular carcinoma. We use human hepatocellular carcinoma cell line HepG2 and human hepatocellular carcinoma xenograft in nude mice as models to study the action of matrine in hepatocellular cancers. We found that caspase-dependent and -independent Program Cell Death (PCD) occurred in matrine-treated HepG2 cells, accompanied by the decreasing of mitochondrial transmembrane potential and the increasing ROS production. Further studies showed that AIF released from the mitochondria to the nucleus, and silencing of AIF reduced the caspase-independent PCD induced by matrine. What’s more, AIF nuclear translocation, and the subsequent cell death as well, was prevented by Bid inhibitor BI-6C9, Bid-targeted siRNA and ROS scavenger Tiron. In the in vivo study, matrine significantly attenuated tumor growth with AIF release from mitochondria into nucleus in nude mice. These data imply that matrine potently induce caspase-independent PCD in HepG2 cells through Bid-mediated AIF translocation.

MicroRNA-500a Promotes the Progression of Hepatocellular Carcinoma by Post-Transcriptionally Targeting BID

“…tBID enhances apoptosis via the mitochondrial pathway [28] only in specific types of cell, namely, CD95 type I cells [29]. Some studies have shown that apoptosis in HepG2 and SMMC-7721 [30,31] cells was regulated by the tBID-mediated-mitochondrial pathway, which is in accordance with the findings of the present study. The discovery that miR-500a inhibits cell apoptosis by suppressing the tBID-mitochondrial apoptosis pathway adds a new aspect to the regulation of apoptosis by BID.…”

Potentiation of resveratrol-induced apoptosis by matrine in human hepatoma HepG2 cells

“…Recently, its anticancer activity has been extensively investigated; it inhibits proliferation and metastasis and induces apoptosis in a variety of malignant cells (12)(13)(14)(15). It also reduces the occurrence of multidrug-resistant tumor cells induced by chemotherapy and displays synergistic activities with other anticancer agents (16,17).…”

Tumor Inhibition Effects and Mechanisms of Angelica sinensis and Sophorae flavescentis ait Decoction Combined with Cisplatin in Xenograft Mice

“…Extracts from Radix sophorae flavescentis ait can inhibit tumor cell growth through up-regulation of caspase 3, down-regulation of bcl-2 at mRNA and protein levels . Matrine from Radix sophorae flavescentis can cause bid-mediated AIF nuclear translocation inducing caspase-independent apoptosis of human hepatocellular carcinoma cells (Zhou et al, 2014). Matrine can significantly inhibit the proliferation and promote the apoptosis of breast cancer MCF-7 cells in death receptor related pathway through up-regulation of Fas protein, supression of telomerase activity, downregulation of VEGF protein resulting in inhibition of the tumor vascular formation (Li et al, 2013).…”