生物活性

• 描述Necrosis can occur in a highly regulated and genetically controlled manner. Necroptotic susceptibility is probably an intrinsic weakness of cancer. Resibufogenin is a major bioactive compound that belongs to bufadienolide family. It is isolated from toad venom. Resibufogenin decreased the cell viability dose-dependently in HCT116 cells. The clonogenic cell survival assay showed that resibufogenin significantly reduced the number of cell clones as compared to the control group, provided further evidence that resibufogenin is an effective antineoplastic agent through inhibiting cell proliferation. Extensive organelle and cell swelling, cytoplasmic vacuolation were observed in resibufogenin-treated SW480 and HCT116. Intracellular ROS (reactive oxygen species) level was also increased in a dose-dependent manner in resibufogenin treated cells. After administration (i.p.) of resibufogenin at 5 and 10 mg/kg/day in mice for 21 days, the weight of tumor in situ were significantly reduced by 27 and 41%, respectively. Vernier caliper measurement showed that resibufogenin decreased the tumor volume in a dose-dependent manner. The weight loss caused by tumor growth was significantly ameliorated by high dose of resibufogenin. These results provide strong evidence that resibufogenin suppresses tumor growth of CRC (colorectal cancer) and ameliorates the weight loss in tumor-bearing mice. Remarkable increase in levels of PYGL, GLUD1 and GLUL as well as increase of RIP3 in resibufogenin-treated mice compared with the control group suggests that resibufogenin inhibits tumor growth through inducing RIP3-mediated activation of PYGL, GLUD1 and GLUL to induce necroptosis in CRC cells^[3].