Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells

Robert B. Shirley, Ismail Kaddour-Djebbar, Dimpu M. Patel, Vijayabaskar Lakshmikanthan, Ronald W Lewis, M. Vijay Kumar

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The proteasome inhibitor Velcade (bortezomib/PS-341) has been shown to block the targeted proteolytic degradation of short-lived proteins that are involved in cell maintenance, growth, division, and death, advocating the use of proteasomal inhibitors as therapeutic agents. Although many studies focused on the use of one proteasomal inhibitor for therapy, we hypothesized that the combination of proteasome inhibitors Lactacystin (AG Scientific, Inc., San Diego, CA) and MG132 (Biomol International, Plymouth Meeting, PA) may be more effective in inducing apoptosis. Additionally, this regimen would enable the use of sublethal doses of individual drugs, thus reducing adverse effects. Results indicate a significant increase in apoptosis when LNCaP prostate cancer cells were treated with increasing levels of Lactacystin, MG132, or a combination of sublethal doses of these two inhibitors. Furthermore, induction in apoptosis coincided with a significant loss of IKKα, IKKβ, and IKKγ proteins and NFκB activity. In addition to describing effective therapeutic agents, we provide a model system to facilitate the investigation of the mechanism of action of these drugs and their effects on the IKK-NFκB axis.

Original languageEnglish (US)
Pages (from-to)1104-1111
Number of pages8
JournalNeoplasia
Volume7
Issue number12
DOIs
StatePublished - Jan 1 2005

Fingerprint

Prostatic Neoplasms
Proteasome Inhibitors
Apoptosis
Pharmaceutical Preparations
Proteins
Therapeutics
Maintenance
Growth
Bortezomib
benzyloxycarbonylleucyl-leucyl-leucine aldehyde
lactacystin

Keywords

  • Apoptosis
  • Lactacystin
  • MG132
  • Prostate
  • Proteasomal inhibitors

ASJC Scopus subject areas

  • Cancer Research

Cite this

Shirley, R. B., Kaddour-Djebbar, I., Patel, D. M., Lakshmikanthan, V., Lewis, R. W., & Kumar, M. V. (2005). Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells. Neoplasia, 7(12), 1104-1111. https://doi.org/10.1593/neo.05520

Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells. / Shirley, Robert B.; Kaddour-Djebbar, Ismail; Patel, Dimpu M.; Lakshmikanthan, Vijayabaskar; Lewis, Ronald W; Kumar, M. Vijay.

In: Neoplasia, Vol. 7, No. 12, 01.01.2005, p. 1104-1111.

Research output: Contribution to journalArticle

Shirley, RB, Kaddour-Djebbar, I, Patel, DM, Lakshmikanthan, V, Lewis, RW & Kumar, MV 2005, 'Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells', Neoplasia, vol. 7, no. 12, pp. 1104-1111. https://doi.org/10.1593/neo.05520
Shirley RB, Kaddour-Djebbar I, Patel DM, Lakshmikanthan V, Lewis RW, Kumar MV. Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells. Neoplasia. 2005 Jan 1;7(12):1104-1111. https://doi.org/10.1593/neo.05520
Shirley, Robert B. ; Kaddour-Djebbar, Ismail ; Patel, Dimpu M. ; Lakshmikanthan, Vijayabaskar ; Lewis, Ronald W ; Kumar, M. Vijay. / Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells. In: Neoplasia. 2005 ; Vol. 7, No. 12. pp. 1104-1111.
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