title: Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells.
abstract: Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin.
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China.
authors.forename: Guangyang
authors.initials: G
authors.lastname: Weng
authors.affiliation: Department of Hematology, Jiangmen Wuyi Traditional Chinese Medicine Hospital, Jiangmen 529000, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of hemodialysis, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518000, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Hematology, Jiangmen Wuyi Traditional Chinese Medicine Hospital, Jiangmen 529000, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China.
authors.forename: Kunyuan
authors.initials: K
authors.lastname: Guo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002066:Busulfan / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D002066:Busulfan; D003474:Curcumin