Eupalitin induces apoptosis in prostate carcinoma cells through ROS generation and increase of caspase-3 activity
Sarjeel Kaleem1, Sahabjada Siddiqui2, Hefazat Hussain Siddiqui1
1Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, 226026, Uttar Pradesh, India.
Abstract:
Prostate cancer is the second most common malignancy in the human reproductive system. Eupalitin is one of the O-methylated flavonol-exhibited enhanced cancer chemopreventive agents. The current study highlights the structural determination of eupalitin and aims to explore the antitumor activity of eupalitin in human prostate cancer cell (PC3) and its underlying mechanism. Eupalitin structure was determined by using FTIR, (1)H NMR, and (13)C NMR. PC3 cells were treated with increasing concentrations of eupalitin, followed by analysis of the cell viability with an MTT assay. The results demonstrated that eupalitin markedly inhibited the proliferation of PC3 cells in a concentration-dependent manner. The results from fluorescent microscopic analysis of nuclear condensation and intracellular ROS generation determined that eupalitin significantly induced ROS level lead to nuclear apoptosis. Cell cycle analysis revealed that eupalitin-induced cell cycle progression as a percentage of cells in G0/G1 phase decreased whereas S phase increased. Caspase-3 immunofluorescence analysis confirms the efficacy of eupalitin-inducing apoptotic pathway and cell death. Thus, our study is helpful in understanding the mechanism underlying these effects in prostate cancer and it may provide novel molecular targets for prostate cancer therapy.
Insights
Eupalitin demonstrates significant antitumor activity against prostate cancer cells (PC3) by inducing apoptosis and altering cell cycle progression. This study reveals its potential as a novel therapeutic agent for prostate cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Prostate cancer is a prevalent malignancy.
- Eupalitin, an O-methylated flavonol, shows promise as a chemopreventive agent.
Purpose of the Study:
- Determine the antitumor activity of eupalitin in human prostate cancer (PC3) cells.
- Elucidate the underlying molecular mechanisms of eupalitin's action.
Main Methods:
- Structural determination of eupalitin using FTIR, 1H NMR, and 13C NMR.
- In vitro assessment of eupalitin's effect on PC3 cell viability (MTT assay).
- Analysis of apoptosis, ROS generation, cell cycle, and caspase-3 activity.
Main Results:
- Eupalitin significantly inhibited PC3 cell proliferation in a dose-dependent manner.
- Eupalitin induced apoptosis via increased ROS levels and nuclear condensation.
- Eupalitin altered cell cycle progression, decreasing G0/G1 phase and increasing S phase.
- Caspase-3 activation confirmed eupalitin's role in inducing apoptosis.
Conclusions:
- Eupalitin exhibits potent antitumor effects against prostate cancer cells.
- The mechanism involves ROS-mediated apoptosis and cell cycle modulation.
- Eupalitin presents a potential therapeutic strategy for prostate cancer.
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