-(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro

Jill A. Macoska, Shreelekha Adsule, Kwanchanit Tantivejkul, Shaomeng Wang, Kenneth J. Pienta, Cheryl T. Lee

Research output: Research - peer-reviewArticle

Abstract

Dysregulation of Bcl2 family member proteins has been associated with poor chemotherapeutic response in bladder cancer, suggesting that agents targeting these crucial proteins may provide an interventional strategy to slow or halt bladder cancer progression and metastasis. In this study, we investigated whether the cottonseed polyphenol, -(-)gossypol, a BH3 mimetic, can reduce the expression of pro-survival, or increase the expression of pro-apoptotic, Bcl2 family proteins and thereby effectively sensitize otherwise resistant bladder cancer cells to the standard chemotherapeutic drugs gemcitabine, paclitaxel and carboplatin. These studies show that gossypol induced apoptosis in both chemosensitive UM-UC2 and chemoresistant resistant UM-UC9 bladder cancer cells in vitro in a dose and time dependent manner via a caspase mediated death signaling pathway. Moreover, in combined treatments, gossypol synergized with gemcitabine and carboplatin to induce apoptosis in chemoresistant bladder cancer cells. This effect was associated with the down-regulation the Bcl-xl and Mcl-1 pro-survival Bcl2 family proteins and up-regulation of the Bim and Puma BH3-only Bcl2 family proteins. Overall, these studies show that gossypol sensitizes bladder cancer cells to standard chemotherapeutic drugs and may provide a promising new strategy for bladder cancer treatment.

LanguageEnglish (US)
Pages323-331
Number of pages9
JournalPharmacological Research
Volume58
Issue number5-6
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Gossypol
Urinary Bladder Neoplasms
Apoptosis
In Vitro Techniques
Proteins
gemcitabine
Carboplatin
Pharmaceutical Preparations
Puma
Cottonseed Oil
Polyphenols
Protein Transport
Caspases
Paclitaxel
Up-Regulation
Down-Regulation
Neoplasm Metastasis

Keywords

  • -(-)Gossypol
  • Apoptosis
  • Bladder cancer
  • Chemotherapy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Macoska, J. A., Adsule, S., Tantivejkul, K., Wang, S., Pienta, K. J., & Lee, C. T. (2008). -(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro. Pharmacological Research, 58(5-6), 323-331. DOI: 10.1016/j.phrs.2008.09.005

-(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro. / Macoska, Jill A.; Adsule, Shreelekha; Tantivejkul, Kwanchanit; Wang, Shaomeng; Pienta, Kenneth J.; Lee, Cheryl T.

In: Pharmacological Research, Vol. 58, No. 5-6, 11.2008, p. 323-331.

Research output: Research - peer-reviewArticle

Macoska, JA, Adsule, S, Tantivejkul, K, Wang, S, Pienta, KJ & Lee, CT 2008, '-(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro' Pharmacological Research, vol 58, no. 5-6, pp. 323-331. DOI: 10.1016/j.phrs.2008.09.005
Macoska JA, Adsule S, Tantivejkul K, Wang S, Pienta KJ, Lee CT. -(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro. Pharmacological Research. 2008 Nov;58(5-6):323-331. Available from, DOI: 10.1016/j.phrs.2008.09.005
Macoska, Jill A. ; Adsule, Shreelekha ; Tantivejkul, Kwanchanit ; Wang, Shaomeng ; Pienta, Kenneth J. ; Lee, Cheryl T./ -(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro. In: Pharmacological Research. 2008 ; Vol. 58, No. 5-6. pp. 323-331
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