3-acetyl-11-keto-beta-boswellic acid decreases the malignancy of taxol resistant human ovarian cancer by inhibiting multidrug resistance (MDR) proteins function

Biomed Pharmacother. 2019 Aug:116:108992. doi: 10.1016/j.biopha.2019.108992. Epub 2019 May 23.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Above results indicated that AKBA might be a potential compound to reverse MDR in human ovarian cancer.

Keywords: 3-acetyl-11-keto-beta-boswellic acid; Multidrug resistance; Ovarian cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / therapeutic use*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • Paclitaxel