Synergistic Cytotoxic and Clonogenic Effects of Paclitaxel and Allicin in MDA-MB-231 Triple-Negative Breast Cancer Cells

Abstract

Background: Triple-negative breast cancer (TNBC) lacks validated molecular targets and relies on cytotoxic chemotherapy limited by toxicity. Combining paclitaxel with the redox-active garlic compound allicin may permit dose reduction while preserving activity. Objective: To define the in vitro cytotoxic profiles of paclitaxel and allicin, quantify their interaction, and assess the durability of the effect in MDA-MB-231 cells. Methods: Cytotoxicity was measured by MTT assay after 24, 48, and 72 h, and IC₅₀ values were derived by non-linear regression. The interaction was quantified by the combination index (CI) and dose-reduction index (DRI) using the Chou–Talalay method (CompuSyn). Long-term viability was assessed by colony formation. Results: The 72-h IC₅₀ values were 60 nM (paclitaxel) and 170 µM (allicin). The interaction was effect-dependent: synergism (CI<1.0) occurred at low-to-intermediate effect levels (CI=0.649, 0.776, and 0.880 at fractions affected of 0.452, 0.650, and 0.820), with antagonism at higher levels (CI=1.062 and 1.249). The DRI exceeded unity for both agents across the synergistic range (up to 2.82-fold for paclitaxel and 3.39-fold for allicin). In the colony assay, the combination gave the lowest surviving fraction (0.3094 vs. paclitaxel and 0.5353 for allicin; p<0.0001). Conclusions: In MDA-MB-231 cells, paclitaxel and allicin act synergistically at low-to-intermediate effect levels and durably suppress clonogenic survival in vitro, supporting further mechanistic evaluation of allicin as a potential dose-sparing adjunct to paclitaxel in this model.