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

  • Ying Wang
  • Arun K. Rishi
  • Wenjuan Wu
  • Lisa Polin
  • Sunita Sharma
  • Edi Levi
  • Steven Albelda
  • Harvey I. Pass
  • Anil Wali
Article

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.

Keywords

Malignant pleural mesothelioma Curcumin Apoptosis Gene expression 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Ying Wang
    • 1
  • Arun K. Rishi
    • 2
  • Wenjuan Wu
    • 3
  • Lisa Polin
    • 4
  • Sunita Sharma
    • 5
  • Edi Levi
    • 6
  • Steven Albelda
    • 7
  • Harvey I. Pass
    • 8
  • Anil Wali
    • 9
    • 10
  1. 1.John D. Dingell VA Medical Center, Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  2. 2.John D. Dingell VA Medical Center, Departments of Oncology and Internal Medicine, Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  3. 3.John D. Dingell VA Medical Center, Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  4. 4.Departments of Oncology and Internal Medicine, Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  5. 5.John D. Dingell VA Medical Center, Department of Surgery, Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  6. 6.John D. Dingell VA Medical Center, Departments of Pathology and OncologyWayne State UniversityDetroitUSA
  7. 7.Pulmonary, Allergy & Critical Care Division, Abramson Research centerUniversity of Pennsylvania Medical CenterPhiladelphiaUSA
  8. 8.Division of Cardiothoracic SurgeryNew York University Cancer CenterNew YorkUSA
  9. 9.John D. Dingell VA Medical Center, Department of Surgery, Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  10. 10.Center to Reduce Cancer Health DisparitiesNational Cancer Institute, National Institutes of HealthRockvilleUSA

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