Cellular and molecular targets of silibinin, a natural flavonoid, in colorectal cancer prevention and therapy

摘要: Colorectal cancer (CRC) is the second most common cause for cancer-related deaths in Europe and USA. Because of limited efficacy considerable toxicity chemotherapeutic agents, new approaches are needed. The hepatoprotective flavonolignan silibinin major biologically active compound milk thistle (Silybum marianum).The molecular mechanisms anticancer properties CRC were studied an vitro model progression consisting adenocarcinoma cell line SW480 its derived metastatic SW620. Its chemopreventive effects assessed vivo azoxymethane-induced colon carcinogenesis rat. Silibinin induced apoptotic death with activation caspase-3 both lines. expression receptors was upregulated, caspase-8 activated. potential mitochondrial membrane perturbed permitting release cytochrome c caspase-9. Besides extrinsic intrinsic pathway, autophagic response. Combination TRAIL, a promising agent selectively inducing apoptosis cells, synergistic Synergy induction also observed by combination histone deacetylase (HDAC) inhibitors TSA SAHA. In preclinical rat, administration able to reduce half number preneoplastic lesions present colon. conclusion, natural chemoprevention therapy TRAIL/HDAC inhibitors.