title: Curcumin augments the efficacy of antitumor drugs used in leukemia by modulation of heat shock proteins via HDAC6.
abstract: 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. In the present study, we 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. Overexpression of HSPs (27, 70, 90), HSF1, and HDAC6 in leukemia cells were down-regulated by curcumin, and the effects on HSPs 27and 70 were less than that on HSP 90. This resulted in cell cycle arrest at the 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 levels in leukemia cells were quenched by curcumin. A probable association between high ROS level and the overexpression of the tumor markers was established in this study. Thus, curcumin enhanced the efficacy of anti-tumor drugs imatinib-mesylate and cytarabine through the inhibition of the tumor markers.
authors.affiliation: Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India.
authors.forename: Ruma
authors.initials: R
authors.lastname: Sarkar
authors.affiliation: Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India.
authors.forename: Apurba
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata 700 026.
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: NSHM Knowledge Campus Calcutta (Group of Institutions), (WBUT), Calcutta, India.
authors.forename: Raj
authors.initials: R
authors.lastname: Biswas
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Roy
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D018922:HL-60 Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D018384:Oxidative Stress / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D010879:Piperazines; D011743:Pyrimidines; D014157:Transcription Factors; D003561:Cytarabine; D000068877:Imatinib Mesylate; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D003474:Curcumin