Reversal of the multidrug resistance of human ileocecal adenocarcinoma cells by acetyl-11-keto-β-boswellic acid via downregulation of P-glycoprotein signals

• Published in: BioScience Trends Vol. 10; no. 5; pp. 392 - 399
• Main Authors: Xue, Xia, Chen, Fang, Liu, Anxin, Sun, Deqing, Wu, Jing, Kong, Feng, Luan, Yun, Qu, Xianjun, Wang, Rongmei
• Format: Journal Article
• Language: English
• Published: Japan International Research and Cooperation Association for Bio & Socio-Sciences Advancement 01-01-2016
• Subjects: acetyl-11-keto-β-boswellic acid (AKBA); Apoptosis - drug effects; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cell Line, Tumor; Colorectal Neoplasms - metabolism; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Humans; Multidrug resistance (MDR); P-glycoprotein (P-gp); reversal of multidrug resistance; Triterpenes - pharmacology
• ISSN: 1881-7815; 1881-7823
• DOI: 10.5582/bst.2016.01115

Multidrug resistance (MDR) represents a clinical obstacle to cancer chemotherapy since it causes cancer recurrence and metastasis. Acetyl-11-keto-β-boswellic acid (AKBA), an active ingredient derived from the plant Boswellia serrata, has been found to inhibit the growth of a wide variety of tumor cells, including glioma, colorectal cancer, leukemia, human melanoma, hepatocellular carcinoma, and prostate cancer cells. However, the actions of AKBA in multidrug-resistant cancer cells have not been fully elucidated. The current study examined the reversal of MDR by AKBA in a human ileocecal adenocarcinoma cell line with vincristine-induced resistance, HCT-8/VCR. A 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay indicated that cytotoxicity increased drastically and the IC50 of VCR in HCT-8/VCR cells decreased in the presence of AKBA. AKBA had a maximum "fold reversal" of MDR (FR) of 9.19-fold. In addition, HCT-8/VCR cells treated with AKBA and VCR exhibited a higher percentage of apoptotic tumor cells according to flow cytometry. The reversal of MDR by AKBA was evident in an intracellular increase in Rhodamine (Rh123), indicating that the activity of P-glycoprotein (P-gp) was blocked. Furthermore, AKBA inhibited the expression of P-gp and decreased levels of expression of multidrug resistance gene 1 in HCT-8/VCR cells. The current results indicated that AKBA might be a potential agent to reverse MDR in human ileocecal adenocarcinoma.