Differential Effects of Alliin and Allicin on Apoptosis and Senescence in Luminal A and Triple‐negative Breast Cancer: Caspase, ΔΨm, and Pro‐apoptotic Gene Involvement

Breast cancer is the most frequent cancer in women worldwide and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo-sulfur compounds, especially alliin and allicin. Here, we evaluated in luminal A and triple-negative breast cancer cells, the effects of both molecules on cell death and senescence, we also assessed their senolytic potential. MCF-7 (luminal A) and HCC-70 (triple-negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; DeltaPsim was assessed using a JC-10 fluorometric assay kit. Apoptosis-related genes were evaluated by RT-PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (beta-Galactosidase Staining) and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of DeltaPsim, caspases -3, -8 and -9 activation, upregulation of NOXA, P21 and BAK, as well as downregulation of BCL-XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence and did not exhibit pro-apoptotic effects in breast cancer cells.