Boswellic acid sensitizes gastric cancer cells to Cisplatin-induced apoptosis via p53-mediated pathway

Shadia Al-Bahlani*, Ikram A. Burney, Buthaina Al-Dhahli, Safiya Al-Kharusi, Fakhra Al-Kharousi, Amani Al-Kalbani, Ikhlas Ahmed

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cisplatin (CDDP) is an effective anticancer drug for Gastric cancer (GC) that induces apoptosis by altering pro- (p53) and anti-apoptotic (Akt and NFkB) proteins; however, chemoresistance remains a big challenge. Additional compounds with promising anticancer effects such as AKBA (Acetyl-keto-beta boswellic acid) may overcome the resistance. However, its role in CDDP-induced apoptosis in GC has not been studied. This study aimed to examine the effectiveness of AKBA on p53-mediated, CDDP-induced apoptosis in GC cells. AGS and NCI-N87 cells were treated with different concentrations (0, 25, 50, 100 μM) of CDDP and/or AKBA. Methods: P53, Akt and NFkB proteins and apoptosis were assessed by Western blot and flow cytometry. The role of p53 was determined by inhibiting its function via the siRNA approach. Results: The results revealed that CDDP and AKBA significantly increased p53 content in both cells, while Akt and NFkB were significantly decreased. Both compounds significantly induced apoptosis in a dose-dependent manner. AKBA sensitized GC cells to CDDP-induced apoptosis by altering the protein expression. P53 downregulation affected Akt and NFkB proteins with a slight increase in apoptosis induction in the combination treated groups. Conclusions: Altogether, our findings suggest that AKBA enhances GC cell sensitivity to CDDP-induced apoptosis via the p53 pathway.

Original languageEnglish
Article number64
JournalBMC pharmacology & toxicology
Volume21
Issue number1
DOIs
Publication statusPublished - Sep 1 2020
Externally publishedYes

Keywords

  • AKBA
  • Apoptosis and gastric cancer
  • CDDP
  • P53

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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