Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis induced by chemotherapy

Lourdes A. Gomez, Alicia De Las Pozas, Teresita Reiner, Kerry L Burnstein, Carlos Perez-Stable

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Abstract

Chemotherapeutic drugs ideally should take advantage of the differences between transformed and normal cells and induce apoptosis only in cancer cells. One such difference may be the overexpression of cyclin B1 protein in cancer cells, which is required for the proper progression through mitosis. Previously, we showed that treatment of human prostate cancer cells with 2-methoxyestradiol (2-ME) or docetaxel results in an accumulation of cyclin B1 protein and an increase in cyclin B1 kinase activity, followed by induction of apoptotic cell death. Inhibition of cyclin B1 kinase lowers apoptosis induced by 2-ME and docetaxel. In this study, we established a positive correlation between cyclin B1 protein and apoptosis induced by chemotherapy in prostate cancer cells. There is minimal cyclin B1 and induction of apoptosis by chemotherapy in nontransformed cells. LNCaP and PC-3 prostate cancer cells stably overexpressing cyclin B1 are more sensitive to apoptosis induced by chemotherapy. LNCaP cells expressing cyclin B1 small interfering RNA to lower cyclin B1 protein or dominant negative cyclin-dependent kinase 1 to inhibit cyclin B1 kinase show a decrease in apoptosis. Increased sensitivity to apoptosis by overexpression of cyclin B1 may be due to lower Bcl-2, higher p53, and decreased neuroendocrine differentiation. We suggest that a cancer-specific mechanism whereby 2-ME and docetaxel may exert anti-prostate cancer activity is the deregulated activation of cyclin B1 kinase, leading to the induction of apoptotic cell death. Our results also suggest that higher levels of cyclin B1 in prostate cancer cells may be a good prognostic marker for chemotherapy.

Original languageEnglish
Pages (from-to)1534-1543
Number of pages10
JournalMolecular Cancer Therapeutics
Volume6
Issue number5
DOIs
StatePublished - May 1 2007

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Cyclin B1
Prostatic Neoplasms
Apoptosis
Drug Therapy
docetaxel
Phosphotransferases
Proteins
Cell Death
CDC2 Protein Kinase
Neoplasms
Induction Chemotherapy
Mitosis
Small Interfering RNA

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

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Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis induced by chemotherapy. / Gomez, Lourdes A.; De Las Pozas, Alicia; Reiner, Teresita; Burnstein, Kerry L; Perez-Stable, Carlos.

In: Molecular Cancer Therapeutics, Vol. 6, No. 5, 01.05.2007, p. 1534-1543.

Research output: Contribution to journalArticle

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