acetyl-11-ketoboswellic-acid and Carcinogenesis

Recurrence of ovarian cancer is mainly due to multidrug resistance (MDR). 3-acetyl-11-keto-beta-boswellic acid (AKBA) could reverse the multidrug resistance in human ileocecal adenocarcinoma cells, but whether AKBA could modulate acquired MDR in ovarian cancer needs to be elucidated.. The current study examined the effect of AKBA on ovarian cancer MDR using a Taxol resistant human ovarian cancer cell line A2780/Taxol. Cell proliferation, migration and invasion, the intracellular accumulation of Rhodamine 123 and expression of MDR proteins were studiedin vitro. Furthermore, the effect of AKBA on oncogenicity of A2780/Taxol cells in nude mice xenograft model was studied.. The results showed that apart from its cytostatic and apoptosis-induction effect, AKBA could restrain A2780/Taxol cell migration and invasion. In addition, AKBA improved the sensitivity of A2780/Taxol cells to Taxol apparently, and the reversal of MDR by AKBA was evident by increasing intracellular Rhodamine 123 in cells. Furthermore, the anti-cancer potential of AKBA was evidenced as that AKBA treatment significantly slowed tumor growth and decreased the expression of P-gp, LRP, BCRP and MRP.. Above results indicated that AKBA might be a potential compound to reverse MDR in human ovarian cancer.

Topics: Animals; Apoptosis; ATP Binding Cassette Transporter, Subfamily B; Carcinogenesis; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Drug Resistance, Neoplasm; Female; Humans; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Ovarian Neoplasms; Paclitaxel; Triterpenes

Membrane fluidity is the most important physiochemical property of cell membranes and governs its functional attributes. The current investigations were undertaken to understand the potential role of acetyl-11-keto-β-boswellic acid (AKBA), if any, on regulation of membrane dynamics under conditions of benzo(a)pyrene (BaP)-induced lung carcinogenesis in female rats. The animals were divided into five groups which included (I) Normal control, (II) Vehicle treated (olive oil), (III) BaP treated, (IV) AKBA treated and (V) BaP + AKBA treated. BaP was administered at a dose level of 50 mg/kg b.wt. in olive oil orally twice a week for 4 weeks. AKBA was given at a dose level of 50 mg/kg b.wt. in olive oil orally thrice a week for 24 weeks. In addition, AKBA was also administered at a similar dose to BaP-treated animals 4 weeks prior to BaP administration and continued for another 20 weeks. The lipid profile and membrane dynamics were analysed in lung tissue. Total lipids, phospholipids content, membrane fluidity, polarization and order of membrane were significantly (p ≤ 0.001) increased in BaP-exposed animals. However, significant decrease was observed in glycolipids, cholesterol, microviscosity and anisotropy levels compared with normal control animals. Appreciable improvements in above indices were recorded when AKBA was administered to BaP-treated animals. Moreover, the structural variations observed in Fourier-transform infrared spectroscopy spectrum were also normalized in BaP-treated rats with AKBA supplementation. This suggests that the AKBA has a potential role in improving membrane fluidity and associated lipid content in BaP-induced lung carcinogenesis.

Topics: Animals; Benzo(a)pyrene; Body Weight; Carcinogenesis; Female; Fluorescence Polarization; Lipids; Lung Neoplasms; Membrane Fluidity; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Triterpenes