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Genistin modulates high-mobility group box protein 1 (HMGB1) and nuclear factor kappa-B (NF-κB) in
Mohamed A Saleh1,2, Samar A Antar3, Walied Abdo4
1Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, 27272, UAE. mohamed.saleh@sharjah.ac.ae.
Abstract:
Cancer is the world's second-largest cause of death. Although there are numerous cancer treatment options, they are typically uncomfortable owing to side effects and ineffectual due to increased resistance to traditional anti-cancer medications or radiation therapy. A key method in cancer treatment is to target delayed/inhibited inflammation and apoptosis, which are very active areas of research. Natural chemicals originating from plants are of particular interest because of their high bioavailability, safety, few side effects, and, most importantly, cost-effectiveness. Flavonoids have become incredibly common as anti-cancer medications, with promising findings as cytotoxic anti-cancer agents that cause cancer cell death. Isolated compound (genistin) was evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7 and MDA-MB-231). The compound exhibited good cytotoxic activities against both cell lines. In vivo antiproliferative efficacy was also investigated in Ehrlich's ascites carcinoma (EAC). Compared to the control group, genistin revealed a significant decrease in tumor weight, volume, high-mobility group box1 (HMGB1), and nuclear factor-kappa B (NF-κB) contents. On the other hand, B-cell lymphoma 2 (Bcl-2) contents increase suggesting an anti-inflammatory and anti-apoptotic activity through inhibition of HMGB1 signaling and activating the Bcl-2 pathway.
Insights
Genistin, a natural flavonoid, effectively combats breast cancer by inducing cancer cell death and reducing tumor growth. It shows promise as a safe and cost-effective anti-cancer agent by targeting inflammation and apoptosis pathways.
Area of Science:
- Oncology
- Natural Product Chemistry
- Molecular Biology
Background:
- Cancer is a leading cause of death globally, with existing treatments facing challenges like side effects and drug resistance.
- Targeting inflammation and apoptosis are critical research areas for novel cancer therapies.
- Natural compounds, particularly flavonoids, offer potential as safe, cost-effective anti-cancer agents with high bioavailability.
Purpose of the Study:
- To evaluate the in vitro and in vivo anti-cancer properties of the isolated flavonoid, genistin.
- To investigate genistin's effects on breast cancer cell lines and tumor growth in vivo.
- To elucidate the molecular mechanisms underlying genistin's anti-cancer activity, focusing on inflammation and apoptosis pathways.
Main Methods:
- In vitro antiproliferative assays using human breast cancer cell lines (MCF-7 and MDA-MB-231).
- In vivo studies using Ehrlich's ascites carcinoma (EAC) model to assess tumor growth inhibition.
- Measurement of key molecular markers including high-mobility group box1 (HMGB1), nuclear factor-kappa B (NF-κB), and B-cell lymphoma 2 (Bcl-2).
Main Results:
- Genistin demonstrated significant cytotoxic activity against both MCF-7 and MDA-MB-231 breast cancer cell lines in vitro.
- In vivo, genistin treatment led to a significant reduction in tumor weight and volume in the EAC model.
- Genistin decreased HMGB1 and NF-κB levels while increasing Bcl-2 expression, indicating anti-inflammatory and anti-apoptotic effects.
Conclusions:
- Genistin exhibits potent cytotoxic and antiproliferative effects against breast cancer cells.
- The anti-cancer activity of genistin is mediated through the inhibition of HMGB1 signaling and activation of the Bcl-2 pathway, suggesting anti-inflammatory and anti-apoptotic properties.
- Genistin represents a promising natural compound for developing novel, cost-effective cancer therapies.
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