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Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis

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Abstract

Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM.

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Acknowledgments

This study was supported by the department of Veterans Affairs Merit Review grants to AKR and AW, Susan G Komen for the Cure grant to AKR, and MARF support to AW.

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Author notes

  1. Anil Wali

    Present address: Center to Reduce Cancer Health Disparities, National Cancer Institute, National Institutes of Health, 6116 Executive Boulevard, Suite 602, Rockville, MD, 20852, USA

Authors and Affiliations

  1. John D. Dingell VA Medical Center, Karmanos Cancer Institute, Wayne State University, VAMC, 4646 John R., Detroit, MI, 48201, USA

    Ying Wang

  2. John D. Dingell VA Medical Center, Departments of Oncology and Internal Medicine, Karmanos Cancer Institute, Wayne State University, Room B4334, VAMC, 4646 John R., Detroit, MI, 48201, USA

    Arun K. Rishi

  3. John D. Dingell VA Medical Center, Karmanos Cancer Institute, Wayne State University, Room B4325, VAMC, 4646 John R., Detroit, MI, 48201, USA

    Wenjuan Wu

  4. Departments of Oncology and Internal Medicine, Karmanos Cancer Institute, Wayne State University, 110 E. Warren Street, Detroit, MI, 48201, USA

    Lisa Polin

  5. John D. Dingell VA Medical Center, Department of Surgery, Karmanos Cancer Institute, Wayne State University, VAMC, 4646 John R., Detroit, MI, 48201, USA

    Sunita Sharma

  6. John D. Dingell VA Medical Center, Departments of Pathology and Oncology, Wayne State University, VAMC, 4646 John R., Detroit, MI, 48201, USA

    Edi Levi

  7. Pulmonary, Allergy & Critical Care Division, Abramson Research center, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    Steven Albelda

  8. Division of Cardiothoracic Surgery, New York University Cancer Center, New York, USA

    Harvey I. Pass

  9. John D. Dingell VA Medical Center, Department of Surgery, Karmanos Cancer Institute, Wayne State University, Room B4325, VAMC, 4646 John R., Detroit, MI, 48201, USA

    Anil Wali

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  1. Ying Wang
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  2. Arun K. Rishi
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Correspondence to Arun K. Rishi.

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Wang, Y., Rishi, A.K., Wu, W. et al. Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem 357, 83–94 (2011). https://doi.org/10.1007/s11010-011-0878-2

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  • DOI: https://doi.org/10.1007/s11010-011-0878-2

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