Additive pharmacological interaction between sirtuin inhibitor cambinol and paclitaxel in MCF7 luminal and MDA-MB-231 triple-negative breast cancer cells.

Abstract

Background: Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in women worldwide. Sirtuin inhibitors (SIRTi), belonging to the histone deacetylase inhibitors group (HDIs), are potent epigenetic drugs that have been investigated for therapeutic use in different clinical disorders, including hematological malignancies and solid tumors.

Methods: The influence of cambinol (CAM; SIRTi) used individually or in combination with standard chemotherapeutic paclitaxel (PAX) on viability (MTT assay), proliferation (BrdU assay), induction of apoptosis and cell cycle arrest (FACS analysis) was determined in MCF7 luminal and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The types of pharmacological drug-drug interaction between CAM and PAX were determined by an exact and rigorous pharmacodynamic method-an isobolography, to determine the presence of synergism, addition or antagonism between analyzed drugs using a variety of fixed-dose ratios.

Results: The combination of CAM and PAX at a fixed ratio of 1:1 exerted additive interaction in the viability of MCF7 and MDA-MB-231 BC cells. Both active agents used separately reduced viability and proliferation of BC cells as well as induced apoptosis and cell cycle arrest. These effects were much more evident in MCF7 than in MDA-MB-231 BC cells. Additionally, CAM combined with PAX increased anti-cancer activity compared to PAX used alone.

Conclusion: CAM might be considered a potential therapeutic agent individually or in combined therapy with PAX against luminal or TNBC.