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Achyrocline satureioides compounds, achyrobichalcone and 3‐ O ‐methylquercetin, induce mitochondrial dysfunction and apoptosis in human breast cancer cell lines
Author(s) -
Bianchi Sara E.,
Pegues Melissa A.,
Dias Camila K.,
Mascia Francesca,
Doneda Eduarda,
Pittol Vanessa,
Rao V. Ashutosh,
Klamt Fábio,
Bassani Valquiria L.
Publication year - 2020
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2348
Subject(s) - cytotoxic t cell , apoptosis , cell culture , biology , in vitro , in vivo , cancer cell , caspase , chemistry , programmed cell death , cancer , pharmacology , biochemistry , cancer research , genetics
Abstract Natural products are a valuable source of new molecules and are important for drug discovery. Many chemotherapeutics currently in clinical use were originated from natural sources and are effective cytotoxic agents. In this study, we investigated the cytotoxic and pro‐apoptotic effects of achyrobichalcone (ACB) and 3‐ O ‐methylquercetin (3 O MQ), two novel compounds isolated from the Achyrocline satureioides plant. Because extracts from this plant have been shown to have anticancer activity in vitro, we evaluated ACB and 3 O MQ using a human breast cancer cell line, MDA‐MB‐231, and a nontumorigenic human breast epithelial cell line, MCF‐12A. We found that ACB demonstrates cytotoxic effects on MDA‐MB‐231 cells, but not MCF‐12A cells. 3 O MQ also demonstrated cytotoxic effects on MDA‐MB‐231 cells, but with lower selectivity compared to treated MCF‐12A cells. Cell death by both compounds was associated with caspase‐9 and caspase‐3/7 activation. Using high‐resolution respirometry, we found that ACB and 3 O MQ were able to cause acute mitochondrial dysfunction in MDA‐MB‐231‐treated cells. These results suggest that apoptosis in MDA‐MB‐231 cells is induced through the activation of the mitochondrial‐dependent pathway. Collectively, these findings suggest that ACB is a strong candidate for further anticancer in vivo tests.