3,5,7‐trihydroxyflavone restricts proliferation of androgen‐independent human prostate adenocarcinoma cells by inducing ROS‐mediated apoptosis and reduces tumour growth

Author:

Raza Waseem12,Meena Abha13ORCID,Luqman Suaib13ORCID

Affiliation:

1. Bioprospection and Product Development Division CSIR‐Central Institute of Medicinal and Aromatic Plants Lucknow Uttar Pradesh India

2. Jawaharlal Nehru University New Delhi India

3. Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India

Abstract

AbstractFlavonoids are among the largest groups of secondary metabolites. Studies suggest that dietary intake of flavonoids reduces the risk of cancer. 3,5,7‐trihydroxyflavone (THF) belongs to the flavone class of flavonoids and potentially inhibits the growth of many cancers; however, it is unexplored in prostate cancer. This study reports the antiproliferative potential of THF in prostate cancer cell line via reactive oxygen species (ROS)‐mediated cascades and examines the tumour reduction potential in swiss albino mice. The potency of THF was evaluated by employing cytotoxicity assays and wound healing assays. Cell cycle, ROS, mitochondrial membrane potential (MMP), and Annexin‐V‐FITC assay were performed using a flow cytometer. In vivo, anticancer potential was achieved using the mice Ehrlich Ascites Carcinoma (EAC) model. THF inhibits cell growth with IC50 of 64.30 µM (MTT), 81.22 µM (NRU) and 25.81 µM (SRB), substantiated by cell migration assay. Cell‐cycle analysis revealed that THF increases the subdiploid population. Furthermore, the Annexin‐V‐FITC assay evoked a significant induction of late apoptosis at a higher concentration of THF. THF also disrupts MMP, caused by an increased generation of ROS. In the EAC model, THF significantly inhibits tumour growth and increases the percent survival of mice and ROS levels in EAC cells. Hence, it may be concluded that THF might execute its antiproliferative effect via inducing ROS generation and could be a promising lead for preclinical and clinical validations.

Funder

Central Institute of Medicinal and Aromatic Plants

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Toxicology,Molecular Biology,Molecular Medicine,Biochemistry,General Medicine

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