Chemotherapy is the preferred choice for treatment of advance breast cancer (BrCa). In most cases, cytotoxic drugs are used at or near a maximum tolerated dose (MTD) to achieve maximum response and eradicate the neoplastic cells, at the same time MTD doses are often toxic and have severe side effects. Lower dose i.e. “optimal biological response modifier dose” (OBRMD) provides potentially beneficial responses, but is not capable of achieving optimal clinical response. Hence, the focus of this study was to achieve the optimal therapeutic outcome of Docetaxel (DTX) at a lower dose by using it in combination with Apigenin (API), a dietary flavonoid present in fruits and vegetables. Effect of DTX and API, either alone or in combination on BrCa cells viability and apoptosis was determined by MTT assay and flow cytometry, respectively. We further investigated the mechanism of enhanced efficacy of DTX using western blot analysis and real time qPCR. Significant decrease in cell viability was observed when cells were treated with low dose DTX in combination with API as compared to either of the agent used individually in MDA-MB-231, MDA-MB-468 and MCF 10A cells. Real time analysis showed that API up regulates pro-apoptotic molecules and down regulates anti-apoptotic molecules when using in combination with DTX. These findings suggest that Apigenin is capable of reducing the effective dose of docetaxel. Hence, this new modality may have better therapeutic outcome with minimal or no toxicity.

Citation Format: Jeronay King, Hina Mir, Neeraj Kapur, Shailesh Singh. Improving therapeutic efficacy of Docetaxel in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3499. doi:10.1158/1538-7445.AM2015-3499