Boswellic acid sensitizes gastric cancer cells to Cisplatin-induced apoptosis via p53-mediated pathway
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(2020) 21:64
RESEARCH ARTICLE
Open Access
Boswellic acid sensitizes gastric cancer cells to Cisplatin-induced apoptosis via p53mediated pathway Shadia Al-Bahlani1*†, Ikram A. Burney2†, Buthaina Al-Dhahli1, Safiya Al-Kharusi1, Fakhra Al-Kharousi1, Amani Al-Kalbani1 and Ikhlas Ahmed3
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 NCIN87 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. Keywords: P53, CDDP, AKBA, Apoptosis and gastric cancer
Background Gastric cancer (GC) is the fourth most common cancer and the 3rd most common cause of cancer-related mortality worldwide [1, 2]. Its incidence varies with geographical regions, for example, the incidence is 20 times higher in Japan, Chile and Costa Rica compared to North America and the Northern Europe [3]. GC is one of the 10 most common cancers in Oman [4]. Cisplatin * Correspondence: [email protected] † Shadia Al-Bahlani and Ikram A. Burney contributed equally to this work. 1 Department of Allied Health Sciences, College of Medicine and Health Sciences, Sultan Qaboos University, P. O. Box 35, PC 123 AlKhoud, Muscat, Oman Full list of author information is available at the end of the article
(Cis–diammine dichloro platinumor; CDDP) and its derivatives remain the standard of care in the treatment of GC. CDDP causes damage to the cancer cells by exerting cytotoxic effects on DNA replication through crosslinking, eventually resulting in apoptosis [5, 6]. Although CDDP is effective initially, eventually tumors develop resistance due to an increase in DNA repair or elevated levels of glutathione, which neutralizes the reactive oxygen species formed by CDDP [7]. CDDP induces apoptosis by activating the p53mediated apoptotic pathway. Factors that activate p53 protein include internal and exte
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