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ISSN Druckformat: 0731-8898
ISSN Online: 2162-6537
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Curcumin Augments the Efficacy of Antitumor Drugs Used in Leukemia by Modulation of Heat Shock Proteins Via HDAC6
ABSTRAKT
Heat shock proteins (HSPs) and Histone deacetylase 6 (HDAC6) are induced under oxidative stress which promotes oncogenesis. HSPs are regulated by Heat shock factor1 (HSF1). HDAC6, a class IIb deacetylase, plays an essential role in tumorigenesis and cell stress response. HSPs, HSF1 and HDAC6 are up-regulated in cancer. Present study explored the effect of curcumin, a phytochemical on HSPs (27, 70, 90), HSF1 and HDAC6 in two different leukemia cell lines (K-562 and HL-60). The association between HDAC6, HSPs and intrinsic oxidative stress was also investigated. Over-expression of HSPs (27, 70, 90), HSF1, and HDAC6 in leukemia cells were down-regulated by curcumin. Effect on HSPs 27and 70 was less than that in HSP 90. This resulted in cell cycle arrest at G2/M stage leading to apoptosis. Different cell cycle regulatory proteins (p53, p21, Cyclin B1, CDK1, Cdc25C) and some apoptosis related proteins (Bcl-2, Bax, Bid, Bad, Apaf1, AIF and Cyt c) were altered by curcumin. Increased ROS level in leukemia cells were quenched by curcumin. A probable association between high ROS level and over-expression of the tumor markers was established in this study. Thus, curcumin enhanced the efficacy of anti-tumor drugs imatinib-mesylate and cytarabine through inhibition of the markers.
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