Anticancer activity of pristimerin in ovarian carcinoma cells is mediated through the inhibition of prosurvival Akt/NF-κB/mTOR signaling

Xiaohua Gao, Yongbo Liu, Dorrah Deeb, Ali Syed Arbab, Subhash C. Gautam

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pristimerin is a quinonemethide triterpenoid that has shown anticancer activity against some cancer types. However, the antitumor effects of pristimerin (PM) in ovarian cancer cells have not been adequately studied. The objective of the present study was to determine the anticancer activity and its mechanism of action in human ovarian carcinoma cell lines. PM strongly inhibited the proliferation of ovarian cancer cells by inducing apoptosis characterized by increased annexin V-binding, cleavage of poly (ADPribose) polymerase (PARP-1) and procaspases-3, -8 and -9. Furthermore, PM caused mitochondrial depolarization. Western blot analysis showed inhibition of prosurvival phospho-AKT (p-AKT), nuclear factor kappa B (NF-κB) (p65) and phospho- mammalian target of rapamycin (p-mTOR) signaling proteins in cells treated with PM. Treatment with PM also inhibited the expression of NF-κB-regulated antiapoptotic Bcl-2, Bcl-xL, c-IAP1 and survivin. Thus, our data showing potent antiproliferative and apoptosis-inducing activity of PM in ovarian carcinoma cells through the inhibition of AKT/NF-κB/mTOR signaling pathway warrant further investigation of PM for the management of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalJournal of Experimental Therapeutics and Oncology
Volume10
Issue number4
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

NF-kappa B
Carcinoma
Ovarian Neoplasms
TOR Serine-Threonine Kinases
Apoptosis
Poly(ADP-ribose) Polymerases
pristimerin
Caspase 8
Annexin A5
Caspase 3
Western Blotting
Cell Line

Keywords

  • Akt
  • Apoptosis
  • Nf-κb
  • Ovarian cancer
  • Pristimerin
  • mTOR

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

Anticancer activity of pristimerin in ovarian carcinoma cells is mediated through the inhibition of prosurvival Akt/NF-κB/mTOR signaling. / Gao, Xiaohua; Liu, Yongbo; Deeb, Dorrah; Arbab, Ali Syed; Gautam, Subhash C.

In: Journal of Experimental Therapeutics and Oncology, Vol. 10, No. 4, 01.01.2014, p. 275-283.

Research output: Contribution to journalArticle

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