Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 5, pp 999–1003 | Cite as

C6 ceramide potentiates curcumin-induced cell death and apoptosis in melanoma cell lines in vitro

  • Teng Yu
  • Jinchao Li
  • Hui Sun
Short Communication

Abstract

Purpose

The majority of metastatic melanomas are resistant to diverse chemotherapeutic agents, and long-term survival for patients with melanoma who have metastatic disease is dismal. Consequently, the search for novel anti-melanoma agents is urgent. Here, we evaluate the potential effects of C6 ceramide to sensitize melanoma cell lines (B16 and WM-115 cells) to curcumin-induced cell death.

Methods

MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to test melanoma cell viability in vitro. Hoechst 33342 fluorescence and Histone DNA ELISA was used to evaluate melanoma cell apoptosis. Apoptosis-associated proteins in melanoma cells after treatments were measured by Western blot.

Results

C6 ceramide promotes curcumin-induced cell death and apoptosis in B16 and WM-115 melanoma cell lines. Curcumin itself promotes pro-apoptosis protein Caspase 3 and Caspase 9 cleavage and anti-apoptosis protein Bcl-XL and X-IAP degradation, and combination of C6 ceramide with curcumin dramatically enhances it. Caspase inhibitors largely inhibit C6-ceramide plus curcumin induced cell death and apoptosis.

Conclusion

We suggest that C6 ceramide sensitizes melanoma cell to curcumin induced cell death and apoptosis in vitro, which is due to, at least in part, the augment of mitochondria apoptosis pathway. Combining C6 ceramide with traditional chemotherapy drugs such as curcumin may have potential to be used as a new therapeutic intervention against melanoma.

Keywords

Curcumin C6 ceramide Apoptosis Chemotherapy Melanoma 

References

  1. 1.
    Auzenne E, Leroux ME, Hu M, Pollock RE, Feig B, Klostergaard J (1998) Cytotoxic effects of sphingolipids as single or multi-modality agents on human melanoma and soft tissue sarcoma in vitro. Melanoma Res 8:227–239CrossRefPubMedGoogle Scholar
  2. 2.
    Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF (2001) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648PubMedGoogle Scholar
  3. 3.
    Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA, Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A (2001) Prognostic factors analysis of 17, 600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634PubMedGoogle Scholar
  4. 4.
    Bill MA, Bakan C, Benson DM Jr, Fuchs J, Young G, Lesinski GB (2009) Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines. Mol Cancer Ther 8:2726–2735CrossRefPubMedGoogle Scholar
  5. 5.
    Bush JA, Cheung KJ Jr, Li G (2001) Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 271:305–314CrossRefPubMedGoogle Scholar
  6. 6.
    Cao C, Huang X, Han Y, Wan Y, Birnbaumer L, Feng GS, Marshall J, Jiang M, Chu WM (2009) Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway. Sci Signal 2:ra17Google Scholar
  7. 7.
    Deshpande D, Devalapally H, Amiji M (2008) Enhancement in anti-proliferative effects of paclitaxel in aortic smooth muscle cells upon co-administration with ceramide using biodegradable polymeric nanoparticles. Pharm Res 25:1936–1947CrossRefPubMedGoogle Scholar
  8. 8.
    Koh HK (1991) Cutaneous melanoma. N Engl J Med 325:171–182CrossRefPubMedGoogle Scholar
  9. 9.
    Marin YE, Wall BA, Wang S, Namkoong J, Martino JJ, Suh J, Lee HJ, Rabson AB, Yang CS, Chen S, Ryu JH (2007) Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Melanoma Res 17:274–283CrossRefPubMedGoogle Scholar
  10. 10.
    Myrick D, Blackinton D, Klostergaard J, Kouttab N, Maizel A, Wanebo H, Mehta S (1999) Paclitaxel-induced apoptosis in Jurkat, a leukemic T cell line, is enhanced by ceramide. Leuk Res 23:569–578CrossRefPubMedGoogle Scholar
  11. 11.
    Qiu L, Zhou C, Sun Y, Di W, Scheffler E, Healey S, Wanebo H, Kouttab N, Chu W, Wan Y (2006) Paclitaxel and ceramide synergistically induce cell death with transient activation of EGFR and ERK pathway in pancreatic cancer cells. Oncol Rep 16:907–913PubMedGoogle Scholar
  12. 12.
    Radin NS, Shayman JA, Inokuchi J (1993) Metabolic effects of inhibiting glucosylceramide synthesis with PDMP and other substances. Adv Lipid Res 26:183–213PubMedGoogle Scholar
  13. 13.
    Rigel DS, Friedman RJ, Kopf AW (1996) The incidence of malignant melanoma in the United States: issues as we approach the 21st century. J Am Acad Dermatol 34:839–847CrossRefPubMedGoogle Scholar
  14. 14.
    Wang L, Shen Y, Song R, Sun Y, Xu J, Xu Q (2009) An anticancer effect of curcumin mediated by down-regulating phosphatase of regenerating liver-3 expression on highly metastatic melanoma cells. Mol Pharmacol 76:1238–1245CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of DermatologyJining First People’s HospitalJiningPeople’s Republic of China
  2. 2.Department of DermatologyThird Hospital of Hang ZhouHangzhouPeople’s Republic of China
  3. 3.Central LabJining First People’s HospitalJiningPeople’s Republic of China

Personalised recommendations