3,5,7-trihydroxyflavone restricts proliferation of androgen-independent human prostate adenocarcinoma cells by
Waseem Raza1,2, Abha Meena1,3, Suaib Luqman1,3
1Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India.
Abstract:
Flavonoids 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.
Insights
3,5,7-trihydroxyflavone (THF) shows antiproliferative effects against prostate cancer cells by increasing reactive oxygen species (ROS). This flavonoid also reduced tumor growth in mice, suggesting its potential for cancer treatment development.
Area of Science:
- Biochemistry
- Pharmacology
- Cancer Research
Background:
- Flavonoids are abundant secondary metabolites with potential anticancer properties.
- 3,5,7-trihydroxyflavone (THF), a flavone, has shown promise against various cancers but remains unexplored in prostate cancer.
- Dietary flavonoid intake is linked to reduced cancer risk.
Purpose of the Study:
- To investigate the antiproliferative potential of 3,5,7-trihydroxyflavone (THF) in prostate cancer.
- To elucidate the mechanisms underlying THF's anticancer effects, focusing on reactive oxygen species (ROS) and apoptosis.
- To evaluate THF's tumor reduction capabilities in a preclinical mouse model.
Main Methods:
- Cytotoxicity assays (MTT, NRU, SRB) and wound healing assays were used to assess THF's potency.
- Flow cytometry was employed to analyze cell cycle, ROS generation, mitochondrial membrane potential (MMP), and apoptosis (Annexin-V-FITC assay).
- Anticancer efficacy was evaluated in vivo using the Ehrlich Ascites Carcinoma (EAC) mouse model.
Main Results:
- THF demonstrated significant antiproliferative activity with IC50 values ranging from 25.81 to 81.22 µM across different assays.
- THF treatment led to cell cycle arrest, increased late apoptosis, and disruption of MMP, correlating with elevated ROS levels.
- In vivo studies showed that THF significantly inhibited tumor growth, enhanced survival rates in EAC-bearing mice, and increased ROS levels in tumor cells.
Conclusions:
- 3,5,7-trihydroxyflavone (THF) exhibits potent antiproliferative effects on prostate cancer cells, likely mediated by ROS generation and induction of apoptosis.
- THF demonstrates significant anticancer potential in vivo, warranting further investigation for clinical applications.
- THF represents a promising candidate for preclinical and clinical validation as an anticancer therapeutic agent.
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