HUHS1015 PROMOTES AUTOPHAGIC XIAP DEGRADATION TO INDUCE APOPTOSIS OF GASTROINTESTINAL CANCER CELLS
| Main Author: | Tomoyuki Nishizaki* |
|---|---|
| Format: | Article Journal |
| Terbitan: |
, 2016
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/59821 |
Daftar Isi:
- The present study aimed at understanding the mechanism underlying HUHS1015-induced apoptosis of MKN45 gastric cancer and Caco-2 colonic cell, Apoptosis, cancer cell lines. HUHS1015 apparently reduced presence of mRNA protein of X-linked inhibitor of apoptosis protein (XIAP) in a treatment time Autophagy (10-60 min)-dependent manner. The reduction of XIAP protein was prevented by the autophagy inhibitors 3-methyladenine and bafilomycin A1. XIAP knock-down significantly activated caspase-3 and reduced cell viability in MKN45 and Caco-2 cells. In the flow cytometry using propidium iodide (PI) and annexin V-FITC (AV), XIAP knock-down significantly increased the proportions of PI-positive/AV-negative, PI-negative/AV-positive, and PI-positive/AV-positive cells, which corresponds to primary necrosis, early apoptosis, and late apoptosis/secondary necrosis, respectively, in both the cell lines. Taken together, the results of the present study indicate that HUHS1015 promotes autophagic XIAP degradation in MKN45 and Caco-2 cells, thereby neutralizing caspase-3 inhibition due to XIAP, to activate caspase-3 and induce apoptosis.