title: Indirubin-3'-monoxime promotes autophagic and apoptotic death in JM1 human acute lymphoblastic leukemia cells and K562 human chronic myelogenous leukemia cells.
abstract: Indirubin is the active component of Dang gui Long hui Wan, a traditional Chinese herbal medicine used as therapy for chronic myelogenous leukemia (CML). In clinical studies, indirubin seldom caused major side-effects. However, the functional effect of indirubin on acute lymphoblastic leukemia (ALL) is unclear. Therefore, we investigated the effects of indirubin-3'-monoxime (I3M) on the ALL cell line JM1 and the CML cell line K562 (control). The anti-leukemia effects and mechanisms of I3M were similar on ALL and CML cells. I3M significantly and dose-dependently decreased cell viability. The G2/M cell cycle phase was arrested and the sub-G1 proportion was relatively increased. In addition, caspase-3 activation led to poly(ADP-ribose) polymerase (PARP)-1 cleavage and the progression of apoptosis. Notably, I3M induced autophagy. However, I3M had no effect on necrosis in either cell line. We specifically found that I3M only marginally affected the survival of primary mature lymphocytes, and was not cytotoxic to granulocytes. Since I3M induced apoptosis and autophagy in human lymphocytic leukemia cells and caused few side-effects in healthy lymphocytes and granulocytes, I3M may be useful for clinical anti-ALL therapy.
authors.affiliation: Department of Hematology and Oncology, Ditmanson Medical Foundation Chia‑Yi Christian Hospital, Chiayi, Taiwan, ROC.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lee
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liu
authors.forename: Ming-Ho
authors.initials: MH
authors.lastname: Chen
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Wu
authors.forename: Hsing-Ying
authors.initials: HY
authors.lastname: Ho
authors.forename: Qwa-Fun
authors.initials: QF
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Chuang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D010091:Oximes / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D007211:Indoles; D010091:Oximes; C474021:indirubin-3'-monoxime; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3