Abstract 2107: Tetra-arsenic hexoxide induces G2/M cell cycle arrest, apoptosis, and autophagy via p38 MAPK- and AKT-mediated pathways in SW620 human colon cancer cells

Tetraarsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980’s. Evidence suggests that As4O6 show anti-cancer effects, whose mechanisms are different from those for As2O3. However, the detailed anticancer mechanism is still unclear. Here, we investigated the anticancer effects of As4O6 on SW620 human colon cancer cells. As4O6 induced cell death in a dose-dependent manner. Flow cytometry analysis revealed that As4O6 increased the sub-G1 (apoptotic cell population) and G2/M phase population in a dose-dependent manner. Further, nuclear condensation and cleaved nuclei were also observed upon staining with Hoechst 33342 in As4O6-treated SW620 cells. Western blot revealed that As4O6 significantly down-regulated the cyclin B1, cdc 2, pro-caspases -3, -8 and -9, and up-regulated p21 and cleavage of PARP in SW620 cells. In addition, As4O6 increased the expression of death receptor 5 (DR5), suppressed Bcl-2 and XIAP family proteins, and promoted the conversion of LC3-I to LC3-II in a Beclin-1 independent manner. Interestingly, As4O6 dephosphorylated Akt and JNK and phosphorylated p38 MAPK, and the cell death was inhibited by p38 MAPK inhibitor; whereas Akt inhibitor augmented the As4O6 induced cell death, suggesting p38 MAPK and AKT were associated with As4O6-induced cell death. Taken together, these findings suggest that As4O6 induced G2/M arrest, apoptosis and autophagic cell death at least in part through p38 MAPK and AKT pathways in SW620 human colon cancer cells. This study may explain the anecdotal anticancer effects showing central necrosis with dormant status of cancers when treated by As4O6 as folk remedy. Citation Format: Won Sup Lee, Jeong Won Yun, Min Jeong Kim, Arulkumar Nagappan, Jing Nan Lu, Seong-Hwan Chang, Jae-Hoon Jeong, GonSup Kim, Jin-Myung Jung, Soon Chan Hong. Tetra-arsenic hexoxide induces G2/M cell cycle arrest, apoptosis, and autophagy via p38 MAPK- and AKT-mediated pathways in SW620 human colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2107. doi:10.1158/1538-7445.AM2017-2107