Alpha fetoprotein is a novel protein‐binding partner for caspase‐3 and blocks the apoptotic signaling pathway in human hepatoma cells

• DOI: 10.1002/ijc.24272
• Publication Date: 2009-01-21T16:25:04Z
• Authors: Mengsen Li; Hui Li; Chaoying Li; Sheng Zhou; Liyuan Guo; Han Liu; Wei Jiang; Xinhua Liu; Pingfeng Li; Michael A. McNutt; Gang Li
• Keywords: Caspase 8; Alpha-fetoprotein

Although there is increasing evidence that alpha fetoprotein (AFP) may function as regulatory factor in the growth of tumor cells, precise mechanism still unclear. In current study, we investigated role cytoplasmic AFP caspase-3-mediated signaling apoptosis. Our results showed low doses TNF-related apoptosis-inducing ligand (TRAIL) elevated activity caspase-8, but not caspase-3. Caspase-3 colocalized and interacted with cytoplasm Bel 7402 translocated into nuclei association occurrence apoptosis while cells were under cotreatment all-trans retinoic acid (ATRA) or TRAIL. was able to form complexes caspase-3 block onward transmission from caspase-8. Knockdown increased sensitivity TRAIL, thereby, triggered signaling. No intermolecule interaction occurred between nor caspase-8 altered after knockdown, demonstrating selectivity interfering apoptotic pathway. The effect on further confirmed by transfection gene HLE (AFP negative). We conclude ATRA TRAIL resistance producing hepatoma at least, part, attributable high level AFP. Therefore, it possible combination silencing together ATRA/TRAIL will benefit enhancement chemotherapeutic efficiency these agents tumors.