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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
Author(s) -
RosasGonzález Vida Celeste,
TéllezBañuelos Martha Cecilia,
HernándezFlores Georgina,
BravoCuellar Alejandro,
Aguilar-Lemarroy Adriana,
JaveSuárez Luis Felipe,
Haramati Jesse,
SolorzanoIbarra Fabiola,
OrtizLazareno Pablo Cesar
Publication year - 2020
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12559
Subject(s) - alliin , allicin , apoptosis , cancer research , cancer , breast cancer , cancer cell , viability assay , downregulation and upregulation , triple negative breast cancer , senescence , caspase 3 , chemistry , biology , programmed cell death , pharmacology , biochemistry , microbiology and biotechnology , genetics , gene
Abstract 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 the effects of both molecules on cell death, senescence, and their senolytic potential in luminal A and triple‐negative breast cancer cells. 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 WST‐1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm 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 (β‐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 ΔΨm, caspase‐3, caspase‐8, and caspase‐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.