Abstract 4212: Natural compounds alone and in combination with platinum drugs found to show significant anti-tumour activity against ovarian cancer cell lines

Abstract

Abstract Acquired drug resistance remains major problem in platinum based chemotherapy against ovarian cancer. It is believed that elevated expression of NF-kB and AKT/PKB is one of the prime reasons for acquired drug resistance. Since tumour active natural compounds can dampen NF-kB and AKT/PKB expression, it is thought that platinum drugs in combination with the natural compounds may produce synergism in killing tumor cells. The present study aimed to apply combinations of platinum drugs cisplatin, oxaliplatin, and carboplatin with natural compounds mycophenolic acid, honokiol, cholecalciferol and 6-shogaol to four ovarian cancer cell lines: A2780, A2780CisR, A2780ZD0473R and SKOV-3 towards overcoming drug resistance. IC50 values of single compounds were determined followed by administration of binary combinations. Studies on DNA damage, cellular platinum accumulation, and platinum-DNA binding levels were carried out. Proteomic studies will be done to explore the key proteins involve with drug resistance. Mycophenolic acid (IC50: 1.34-7.83 μM) from Penicillium brevicompactum and 6-shogaol (IC50: 6.79-10.20 μM) from Zingiber officinale showed significant activity against ovarian cancer cell lines. Ginger derived pure compound 6-shogaol showed prominent synergism in combination with platinums when administered as a bolus (0/0h) and with 0/4 h sequence. Honokiol from Magnolia virginia alone and in combination with cisplatin showed significant DNA damage in A2780 cell line whereas cholecalciferol did the same to A2780cisR cell line. Bolus combination of cisplatin and 6-shogoal produced increased cellular platinum accumulation and 3 times more Pt-DNA binding than cisplatin alone treated A2780 cells. Though honokiol and cisplatin (0/0 h) combination have half cellular platinum accumulation in compare to cisplatin alone treated A2780 cells but showed 9 times higher Pt-DNA binding. Cholecalciferol and 6-shogaol in combination with cisplatin also showed promising Pt-DNA in A2780CisR cell line. In conclusion, 6-shogaol, cholecalciferol and honokiol showed significant activity alone and in combination with cisplatin and oxaliplatin against ovarian cancer tumour models. Note: This abstract was not presented at the meeting. Citation Format: Md Sheikh Anwar, Jun Qing Yu, Philip Beale, Fazlul Huq. Natural compounds alone and in combination with platinum drugs found to show significant anti-tumour activity against ovarian cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4212. doi:10.1158/1538-7445.AM2017-4212