In vitro evaluation of dioscin and protodioscin against ER-positive and triple-negative breast cancer

PLoS One. 2023 Feb 9;18(2):e0272781. doi: 10.1371/journal.pone.0272781. eCollection 2023.

Abstract

Women's breast cancer is one of the most significant healthcare issues for the human race that demands a proactive strategy for a cure. In this study, the cytotoxic activity (MTT assay) of two natural steroidal compounds, protodioscin and dioscin, against two major subtypes of human breast cancer estrogen receptor-positive (ER-positive)/MCF-7 and triple-negative breast cancer (TNBC)/MDA-MB-468), was assessed. The clonogenic capacity was evaluated using the clonogenic assay. Oxidative stress was determined by measuring the formation of malondialdehyde and H2O2 and the assessment of total antioxidant enzyme activities (SOD, GPx, GR, and TrxR). Protodioscin and dioscin were highly cytotoxic against the tested cell lines (1.53 μM <IC50< 6 μM) with low cytotoxicity on normal cells (PBMC; IC50 ≥ 50 μM). Interestingly, these compounds were responsible for a substantial decrease in the clonogenic capacity of both cell lines. Moreover, dioscin was able to reduce the cell motility of the invasive breast cancer cells (MDA-MB-468). At the molecular level, the two treatments resulted in an increase of reactive oxygen species. Notably, both compounds were responsible for decreasing the enzymatic activities of glutathione reductase and thioredoxin reductase. On the basis of such considerations, protodioscin and dioscin may serve as promising natural compounds to treat TNBC and ER-positive breast cancer through the induction of oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Antioxidants / pharmacology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Endoplasmic Reticulum / metabolism
  • Female
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Leukocytes, Mononuclear / metabolism
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • dioscin
  • Hydrogen Peroxide
  • protodioscin

Grants and funding

This study was supported by the Lalla Salma Foundation: Prevention and Treatment of Cancer. Research project N° 09/AP 2013 (Rabat-Morocco). The funders of the study had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.