Abstract 4585: Crocin-supplemented cisplatin is highly effective in killing breast cancer cells than cisplatin alone

Abstract

Abstract Breast cancer afflicts women of all ages. Limited treatment options that are currently available include use of hormone antagonists and various platinum-based chemical agents (Cisplatin, Carboplatin and Oxaliplatin). Cisplatin, is a widely used chemotherapeutic drug that is often prescribed for the treatment of hormone resistant breast tumors. Through inter- and intra-strand DNA cross linking, Cisplatin induces apoptosis in cancer cells. Although, it is very effective in its action, the use of Cisplatin is accompanied with high overall toxicity due to its indiscriminate killing of normal cells along with cancer cells; therefore, it has to be used at less than the effective dose. Crocin, is a phytochemical that efficiently kills cancer cells without affecting the normal cells even at higher doses. Due to this property, it is currently being tested as an anti-cancer drug either alone or in combination with various novel and traditional anticancer agents to supplement and even use the otherwise toxic anticancer drugs at a lower dose. In this study, we supplemented Cisplatin with Crocin to reduce the amount of Cisplatin that could kill breast cancer cells. MCF-7 and MDA MB-231 breast cancer cells in culture were initially treated with Cisplatin and Crocin alone for 24, 48 and 72 hours using a spectrum of concentrations for each drug (Cisplatin: 1 to 100ug/ml; Crocin: 0.25 to 10mM) to assess the cell death by MTT assay. The concentration that induced fifty percent killing of the cancer cells was designated as IC50. FACS based Annexin V assay was used to confirm the results obtained from MTT assays. Using isobologram analysis we tested various combinatorial doses of Cisplatin and Crocin that were lower than IC50 to determine the extent of synergism displayed by the drug combinations. The formula used to ascertain the synergy index was: q= I(A+B)/ (IA+IB - IA*IB), where I(A + B) represented the inhibition rate of the Crocin + Cisplatin combination; IA and IB were the inhibition rate of Crocin and Cisplatin individually and respectively. If the drug combination showed q= 0.85 to 1.15, it was considered as simple addictive effect, while a value of q= 1.15 to 2.0, indicated that the drugs were showing a degree of synergism. q= >2.0 indicated significant synergistic effect between the two agents. Experimental data were statistically analyzed to ascertain significant p-value. In our experiments, we could reduce the effective dose of Cisplatin by supplementing it with Crocin, and with this combination, we could achieve enhanced killing of breast cancer cells that was until now only possible with higher doses of Cisplatin, when used alone. These results suggest that cancer patients can benefit from this study as plant based anti-cancer compounds can be used to reduce toxicity from higher doses of traditional anti-cancer drugs, but without compromising their effectiveness. Citation Format: Sachin Gupta, Bhawna Jhamb, Sanjay Katiyar. Crocin-supplemented cisplatin is highly effective in killing breast cancer cells than cisplatin alone. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4585. doi:10.1158/1538-7445.AM2014-4585