2. Academic Validation
  3. A styrylpyrone dimer isolated from Aniba heringeri causes apoptosis in MDA-MB-231 triple-negative breast cancer cells

A styrylpyrone dimer isolated from Aniba heringeri causes apoptosis in MDA-MB-231 triple-negative breast cancer cells

  • Bioorg Med Chem. 2021 Feb 15:32:115994. doi: 10.1016/j.bmc.2021.115994.
Kamylla Fernanda Souza de Souza 1,  Danilo Tófoli 2,  Indiara Correia Pereira 1,  Kelly Juliana Filippin 1,  Ana Tereza Gomes Guerrero 3,  Edgar Julian Paredes-Gamero 1,  Maria de Fatima Cepa Matos 1,  Walmir Silva Garcez 2,  Fernanda Rodrigues Garcez 2,  Renata Trentin Perdomo 4
Affiliations

Affiliations

  • 1 Laboratory of Molecular Biology and Cell Culture, School of Pharmaceutical Sciences, Food Technology, and Nutrition, Universidade Federal de Mato Grosso do Sul, Mato Grosso do Sul, Campo Grande, MS, Brazil.
  • 2 Institute of Chemistry, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil.
  • 3 Fundação Oswaldo Cruz, Campo Grande, MS, Brazil.
  • 4 Laboratory of Molecular Biology and Cell Culture, School of Pharmaceutical Sciences, Food Technology, and Nutrition, Universidade Federal de Mato Grosso do Sul, Mato Grosso do Sul, Campo Grande, MS, Brazil. Electronic address: renata.trentin@ufms.br.
PMID: 33477019 DOI: 10.1016/j.bmc.2021.115994
Abstract

The styrylpyrone dehydrogoniothalamin (1) and two of its dimers (2 and 3) were isolated from the leaves of Aniba heringeri (Lauraceae). Compound 3 is new, while 1 and 2 are being reported for the first time in this species. Structures were determined by 1D- and 2D-NMR spectroscopy, mass spectrometry, and optical rotation data. Cytotoxic effects and selectivity indices were evaluated in five neoplastic cell lines-PC-3 (prostate), 786-0 (renal), HT-29 (colon), MCF-7, and MDA-MB-231 (breast)-and a non-neoplastic cell line, (NIH/3T3, murine fibroblast). Compound 1 inhibited cell growth by 50% (GI50) at concentrations in the 90.4-175.7 μM range, while 2 proved active against MCF-7 and MDA-MB-231 breast cells (GI50 = 12.24, and 34.22 μM, respectively). Compound 3 showed strong cytotoxicity (GI50 = 4.4 μM) against MDA-MB-231 (an established basal triple-negative breast carcinoma (TNBC) cell line), with a high selective index of 35. This compound was subsequently evaluated for Apoptosis induction in MDA-MB-231 cells, using GI50 and 50% lethal concentrations (LC50). Flow cytometry analysis showed that at LC50 compound 3 induced cell death with phosphatidylserine externalization and Caspase-3 activation. Apoptotic genes were measured by RT-qPCR, revealing an upregulation of Bax, with an increase in expression of the Bax/BCL2 ratio in treated cells. Fluorescence microscopy disclosed morphological changes related to Apoptosis. Overall, these findings showed compound 3 to be a promising prototype against TNBC cells that tend to respond poorly to conventional therapies.

Keywords

Apoptosis; Cytotoxicity; Dehydrogoniothalamin dimer; MDA-MB-231; Styrylpyrone dimers.

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