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: Guangyang Weng, Yingjian Zeng, Jingya Huang, Jiaxin Fan, Kunyuan Guo
• Journal: BioMed research international (Biomed Res Int) Vol. 2015 Pg. 630397 ( 2015) ISSN: 2314-6141 [Electronic] United States
• PMID: 26557682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Inhibitor of Apoptosis Proteins
• Survivin
• Busulfan
• Curcumin

Topics

• Apoptosis (drug effects)
• Busulfan (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Curcumin (pharmacology)
• Down-Regulation (drug effects, genetics)
• Drug Synergism
• HL-60 Cells
• Humans
• Inhibitor of Apoptosis Proteins (genetics)
• Leukemia, Myeloid, Acute (drug therapy, genetics)
• Neoplastic Stem Cells (drug effects)
• Survivin