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Cucurbita ficifolia Fruit Extract Induces Tp53/Caspase-Mediated Apoptosis in MCF-7 Breast Cancer Cells
Ghedeir M Alshammari1, Aristatile Balakrishnan1, Ali A Alshatwi1
1Adipocytes and Metabolic Disorders Lab, Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.
Abstract:
The second most biggest cancer worldwide is breast cancer. There is an increasing need for safer, effective, and affordable drug candidates from natural sources to treat breast cancer. In the present investigation, the anticancer effect of Cucurbita ficifolia Bouché (C. ficifolia) fruit extract was tested on the human breast cancer cells such as MCF-7. The cells were exposed with different doses of C. ficifolia, for the assessment of IC50 concentrations on the MCF-7 cell lines for 24 hs. The effect of C. ficifolia fruit extract on morphological and apoptotic changes were evaluated by specific fluorescence staining techniques and real-time PCR in a time-dependent manner for 24 hs and 48 hs. The IC50 value for C. ficifolia fruit extract was found to be 90 μg/mL. Morphological alteration and apoptotic distinctiveness aspect like chromatin condensation and nuclear fragmentation were noticed in C. ficifolia extract exposed breast cancer cells. Further, we observed that C. ficifolia extract-induced programmed cell death in the MCF-7 cells were mediated with the elevated expression of the tumor suppressor gene such as p53 and apoptotic markers such as caspase-8, caspase-9, caspase-3, fatty acid synthase (FAS), Fas-associated protein with death domain (FADD), Bcl-2 homologous antagonist/killer (BAK), and Bcl-2-associated X protein (BAX). These observations established that C. ficifolia significantly concealed the cell division and provoked p53/caspase-mediated programmed cell death. Further, we noticed that this cell death in MCF-7 cells is concentration and time dependent. As evaluated through the comet assay, C. ficifolia induced DNA damage; further upon increasing the duration of the treatment, the DNA damage was higher than before. Thus, our study concludes that C. ficifolia could serve as an effective anticancer agent through vital gene modulation.
Insights
Cucurbita ficifolia fruit extract demonstrated anticancer effects against human breast cancer cells (MCF-7). This natural compound induced programmed cell death and DNA damage, suggesting its potential as an effective anticancer agent.
Area of Science:
- Phytochemistry and Pharmacology
- Cancer Biology and Therapeutics
Background:
- Breast cancer is a leading global health concern, necessitating novel and safe therapeutic agents.
- Natural products offer a promising source for developing affordable and effective anticancer drugs.
Purpose of the Study:
- To investigate the anticancer potential of Cucurbita ficifolia (C. ficifolia) fruit extract on human breast cancer cells (MCF-7).
- To evaluate the cytotoxic effects, morphological changes, and apoptotic mechanisms induced by C. ficifolia extract.
Main Methods:
- MCF-7 cells were treated with varying concentrations of C. ficifolia extract to determine the IC50 value.
- Morphological and apoptotic changes were assessed using fluorescence staining and real-time PCR.
- DNA damage was evaluated using the comet assay.
Main Results:
- The IC50 value of C. ficifolia extract against MCF-7 cells was determined to be 90 μg/mL.
- Extract treatment induced characteristic apoptotic features, including chromatin condensation and nuclear fragmentation.
- C. ficifolia upregulated tumor suppressor genes (p53) and apoptotic markers (caspase-3, -8, -9, FAS, FADD, BAK, BAX), indicating p53/caspase-mediated apoptosis.
- Concentration and time-dependent DNA damage was observed in MCF-7 cells treated with the extract.
Conclusions:
- Cucurbita ficifolia extract exhibits significant anticancer activity against human breast cancer cells.
- The extract effectively induces programmed cell death and DNA damage through modulation of key genes.
- C. ficifolia holds potential as a natural anticancer agent for breast cancer therapy.
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