Arachidin-1, a Prenylated Stilbenoid from Peanut, Induces Apoptosis in Triple-Negative Breast Cancer Cells
Sepideh Mohammadhosseinpour1,2, Linh-Chi Ho2, Lingling Fang2
1Molecular Biosciences Graduate Program, College of Sciences and Mathematics, Arkansas State University, Jonesboro, AR 72467, USA.
Abstract:
Triple-negative breast cancer (TNBC) is unresponsive to typical hormonal treatments, causing it to be one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. The goal of this study was to assess cytotoxicity and apoptosis mechanisms of prenylated stilbenoids in TNBC cells. The prenylated stilbenoids arachidin-1 (A-1) and arachidin-3 (A-3) are analogs of resveratrol (RES) produced in peanut upon biotic stress. The anticancer activity of A-1 and A-3 isolated from peanut hairy root cultures was determined in TNBC cell lines MDA-MB-231 and MDA-MB-436. After 24 h of treatment, A-1 exhibited higher cytotoxicity than A-3 and RES with approximately 11-fold and six-fold lower IC50, respectively, in MDA-MB-231 cells, and nine-fold and eight-fold lower IC50, respectively, in MDA-MB-436 cells. A-1 did not show significant cytotoxicity in the non-cancerous cell line MCF-10A. While A-1 blocked cell division in G2-M phases in the TNBC cells, it did not affect cell division in MCF-10A cells. Furthermore, A-1 induced caspase-dependent apoptosis through the intrinsic pathway by activating caspase-9 and PARP cleavage, and inhibiting survivin. In conclusion, A-1 merits further research as a potential lead molecule for the treatment of TNBC.
Insights
Arachidin-1, a peanut compound, shows potent anticancer effects against triple-negative breast cancer (TNBC) by inducing apoptosis and blocking cell division. This natural molecule offers a promising new avenue for TNBC treatment development.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to its resistance to conventional treatments.
- Developing novel therapeutic strategies is crucial for improving survival rates in TNBC patients.
Purpose of the Study:
- To evaluate the cytotoxic and apoptosis-inducing potential of prenylated stilbenoids, specifically arachidin-1 (A-1) and arachidin-3 (A-3), in TNBC cells.
- To investigate the underlying mechanisms of action for these compounds.
Main Methods:
- Isolation of prenylated stilbenoids (A-1, A-3) from peanut hairy root cultures.
- Assessment of cytotoxicity and IC50 values in TNBC cell lines (MDA-MB-231, MDA-MB-436) and a non-cancerous cell line (MCF-10A).
- Cell cycle analysis and investigation of apoptosis-related markers (caspase-9, PARP, survivin).
Main Results:
- Arachidin-1 demonstrated significantly higher cytotoxicity against TNBC cells compared to arachidin-3 and resveratrol (RES).
- A-1 selectively inhibited TNBC cell proliferation by arresting cells in the G2-M phase, without affecting normal cells.
- A-1 induced apoptosis via the intrinsic pathway, evidenced by caspase-9 activation, PARP cleavage, and survivin inhibition.
Conclusions:
- Arachidin-1 exhibits potent and selective anticancer activity against triple-negative breast cancer.
- A-1's ability to induce apoptosis and arrest cell division warrants further investigation as a potential therapeutic lead for TNBC.
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