title: Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells.
abstract: Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre‑LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin.
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Deparment of Hematology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, P.R. China.
authors.forename: Guangyang
authors.initials: G
authors.lastname: Weng
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Zhangqiu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Affiliated Jiangmen Traditional Chinese Medical Hospital of Jinan University, Jiangmen, Guangdong 529000, P.R. China.
authors.forename: Pingfang
authors.initials: P
authors.lastname: Xia
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, P.R. China.
authors.forename: Kunyuan
authors.initials: K
authors.lastname: Guo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D000077022:Survivin
chemical_list: D001152:Arsenicals; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D010087:Oxides; D034741:RNA, Small Interfering; D000077022:Survivin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D003474:Curcumin; D000077237:Arsenic Trioxide