Saponins of Marsdenia Tenacissima promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria then activating cytochrome C/Caspase-9/Caspase-3 pathway.

Liver cancer is one of the most common cancers in the world and the second leading cause of death in cancer patients. There is an urgent need for an effective and less toxic treatment for liver cancer. Saponins of Marsdenia Tenacissima (SMT) as a potential anticancer drug has attracted extensive attention of researchers because of its effective biological activity. The effect of SMT on HepG2 Li-7 and L-02 cells was detected by CCK8 assay. At the same time, the apoptosis rate was detected by flow cytometer and laser confocal microscope, and the morphological changes of mitochondria were observed under electron microscope. The levels of bax, cytochrome c, caspase-9, caspase-3, cleaved caspase-3 and protein were detected using Western bolt. Finally, BALB/c was subcutaneously injected with H22 cells to form tumors, and SMT was intragastrically injected to detect the size of the transplanted tumor. SMT can induce apoptosis in vitro and reduce the size of transplanted tumor in vivo. Increases the rate of apoptosis through the cytochrome c pathway and regulates the expression of apoptosis-related proteins. These results suggest that SMT may be one of the potential candidates for the treatment of liver cancer.

Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) has therapeutic potential for the treatment of hepatocellular carcinoma (HCC). 5-Fluorouracil (5-Fu) has been a conventional chemotherapeutic agent for HCC. Unfortunately, the nonspecific cytotoxicity and multidrug resistance caused by long-term use limited the clinical efficacy of 5-Fu. This study was aimed to investigate whether the combination of CP-25 and 5-Fu could generate synergistic effect in inhibiting HCC. The experiments on the diethylnitrosamine (DEN) -induced mice showed that compared with applying single drugs, the combination of CP-25 and 5-Fu presented stronger inhibition in tumor nodule and volume. Meanwhile, CP-25 and 5-Fu activated the intrinsic mitochondrial apoptosis pathway induced by P53, inhibited anti-apoptotic B-cell lymphoma (Bcl-2), induced the pro-apoptotic Bcl-2-associated X protein (Bax), Cytochrome-C and caspases. In addition, the synergistic effect was also validated in Bel-7402 and HepG-2 cells in vitro. This research not only provides a novel and effective combination strategy for the therapy of HCC but also provides an experimental basis for the development of CP-25 and 5-Fu compound preparation.