title: Reversal of the multidrug resistance of human ileocecal adenocarcinoma cells by acetyl-11-keto-β-boswellic acid via downregulation of P-glycoprotein signals.
abstract: 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.
authors.affiliation: Department of Pharmacy, the Second Hospital of Shandong University.
authors.forename: Xia
authors.initials: X
authors.lastname: Xue
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Anxin
authors.initials: A
authors.lastname: Liu
authors.forename: Deqing
authors.initials: D
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.forename: Yun
authors.initials: Y
authors.lastname: Luan
authors.forename: Xianjun
authors.initials: X
authors.lastname: Qu
authors.forename: Rongmei
authors.initials: R
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid