The roles of autophagic cell death and apoptosis induced by topoisomerase inhibitor irinotecan in colon cancer cells with
deleted p53 were investigated during 48 h. We report that irinotecan-dependent cytotoxicity and proapoptotic activity were reduced in the
present model while autophagy levels significantly increased. Upon p53 transfection, cell demise rates increased, with cells bearing the
features of apoptosis and autophagic cell death. The subsequent studies into mechanisms of cell death process revealed the important role
of Bax in mediating mitochondrial and lysosomal leakage which might serve as leading signals for both apoptosis and autophagic cell
death. These results suggest that different modes of cell death in p53 null colon cancer cells treated with cytostatics (irinotecan) may be
activated simultaneously. Moreover, their interactions possibly occur at several stages and aren´t mutually exclusive. This might thus lead
to a potential synergism with interesting therapeutic ramifications.
Keywords: Irinotecan, Colon cancer, Autophagy, p53, Chemotherapy, Autophagic cell death, Apoptosis, Bax, Lysosomes, Mitochondria.
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Published on: 30 April, 2013
Page: [811 - 820]