The vascular targeting agent Combretastatin-A4 directly induces autophagy in adenocarcinoma-derived colon cancer cells

摘要: Abstract Recent clinical data demonstrated that the vascular targeting agent Combretastatin-A4 phosphate (CA-4P) prolonged survival of patients with advanced anaplastic thyroid cancer without any adverse side effects. However, as a single CA-4 failed to reduce tumour growth in murine CT-26 adenocarcinoma colon model. Furthermore, molecular mechanism innate resistance HT-29 human cells is largely unknown. In this report, we demonstrate for first time exposure and an azetidinone cis-restricted analogue, CA-432 (chemical name; 4-(3-Hydroxy-4-methoxyphenyl)-3-phenyl-1-(3,4,5-trimethoxyphenyl)-azetidin-2-one) induced autophagy adenocarcinoma-derived CT-26, Caco-2 but not fibrosarcoma-derived HT-1080 cells. Autophagy fundamental self-catabolic process which can facilitate cell spite stress by generating energy via lysosomal degradation cytoplasmic constituents. was confirmed acridine orange staining vesicle formation, electron microscopy increased expression LC3-II. Combretastatin-induced associated loss mitochondrial membrane potential elongation mitochondria. inhibition vacuolar H+ATPase inhibitor Bafilomycin-A1 (BAF-A1) significantly enhanced death. Both its synthetic derivative, formation large hyperdiploid The these polyploid inhibited inhibitor, BAF-A1. Results presented within novel response combretastatin may be manipulated enhance therapeutic efficacy class agents.