Tetraarsenic hexoxide induces G2/M arrest, apoptosis, and autophagy via PI3K/Akt suppression and p38 MAPK activation in SW620 human colon cancer cells

• DOI: 10.1371/journal.pone.0174591
• Publication Date: 2017-03-29T18:02:20Z
• Authors: Arulkumar Nagappan; Won Sup Lee; Jeong Won Yun; Jing Nan Lu; Seong-Hwan Chang; Jae-Hoon Jeong; Gon Sup Kim; Jin-Myung Jung; Soon Chan Hong
• Keywords: LY294002

Tetraarsenic hexoxide (As4O6) has been used in Korean folk medicines for the treatment of cancer, however its anti-cancer mechanisms remain obscured. Here, this study investigated effect As4O6 on SW620 human colon cancer cells. showed a dose-dependent inhibition cells proliferation. significantly increased sub-G1 and G2/M phase population, Annexin V-positive manner. arrest was concomitant with augment p21 reduction cyclin B1, cell division cycle 2 (cdc 2) expressions. Nuclear condensation, cleaved nuclei poly (adenosine diphosphate‑ribose) polymerase (PARP) activation were also observed As4O6-treated induced depolarization mitochondrial membrane potential (MMP, ΔΨm) but not reactive oxygen species (ROS) generation. Further, death receptor 5 (DR5), DR4 suppressed B‑cell lymphoma‑2 (Bcl-2) X-linked inhibitor apoptosis protein (XIAP) family proteins. formation AVOs (lysosomes autophagolysosomes) promoted conversion microtubule-associated 1A/1B-light chain 3 (LC3)-I to LC3-II dose- time- dependent Interestingly, specific phosphoinositide 3-kinase (PI3K)/Akt (LY294002) augmented death; whereas p38 mitogen-activated kinases (p38 MAPK) (SB203580) abrogated death. Thus, present provides first evidence that arrest, autophagic through PI3K/Akt MAPK pathways alteration