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Journal of Environmental Pathology, Toxicology and Oncology
インパクトファクター: 1.625 5年インパクトファクター: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 印刷: 0731-8898
ISSN オンライン: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2014010913
pages 247-263

Curcumin Augments the Efficacy of Antitumor Drugs Used in Leukemia by Modulation of Heat Shock Proteins Via HDAC6

Ruma Sarkar
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India
Apurba Mukherjee
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India
Sutapa Mukherjee
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata 700 026
Raj Biswas
NSHM Knowledge Campus Calcutta (Group of Institutions), (WBUT), Calcutta, India
Jaydip Biswas
Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India
Madhumita Roy
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India

要約

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.

キーワード: HSPs, HSF1, HDAC6, curcumin, ROS, leukemia

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