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Sesamol Upregulates Death Receptors and Acts as a Chemosensitizer in Solid Ehrlich Carcinoma Model in Mice
Nesma A Abd Elrazik1, Mohamed El-Mesery1, Amro El-Karef2
1Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Aims:
The aim of the present study was to investigate the anti-tumor effect of sesamol (SML), a nutritional phenolic compound of sesame, in solid Ehrlich carcinoma (SEC) model in mice and its ability to enhance doxorubicin (DOX) anti-tumor activity. Moreover, we analyzed the ability of SML to protect against DOX-induced cardiotoxicity.
Main Methods:
SML (70 mg/kg), DOX (2 mg/kg) and their combination were given to mice bearing SEC for 21 day. The mRNA level of Fas, FasL, TRAILR2, TRAIL, caspase-3 and Bcl-2 were assessed by qPCR. Tumor and cardiac tissues were examined for histopathological changes by hematoxylin and eosin. Active caspase-3 was scored by immunohistochemical analysis.
Key Findings:
SML treatment significantly decreased solid tumor size and weight. In addition, SML enhanced DOX anti-tumor activity. SML treatment either alone or in combination with DOX induced upregulation of Fas/FasL and TRAILR2/TRAIL gene expression. Moreover, SML increased caspase-3 protein and gene expressions and decreased Bcl-2 gene expression.
Significance:
SML upregulates death receptors expression and enhances apoptosis induction in tumor cells that may explain its anti-tumor activity. Not only that, but SML also enhances DOX anti-tumor activity and attenuates its cardiotoxicity.
Insights
Sesamol (SML), a sesame compound, exhibits anti-tumor effects by increasing apoptosis and enhances doxorubicin (DOX) efficacy. SML also protects against DOX-induced cardiotoxicity, offering a potential therapeutic strategy.
Area of Science:
- Pharmacology
- Cancer Biology
- Natural Products Chemistry
Background:
- Sesamol (SML) is a phenolic compound found in sesame seeds with potential health benefits.
- Doxorubicin (DOX) is a widely used chemotherapy drug, but its efficacy can be limited by cardiotoxicity.
- Investigating natural compounds to enhance chemotherapy and mitigate side effects is crucial in cancer treatment.
Purpose of the Study:
- To evaluate the anti-tumor effects of sesamol (SML) in a solid Ehrlich carcinoma (SEC) mouse model.
- To determine if SML can enhance the anti-tumor activity of doxorubicin (DOX).
- To assess SML's protective effect against DOX-induced cardiotoxicity.
Main Methods:
- Mice with SEC were treated with SML (70 mg/kg), DOX (2 mg/kg), or a combination for 21 days.
- Gene expression of apoptosis markers (Fas, FasL, TRAILR2, TRAIL, caspase-3, Bcl-2) was analyzed using qPCR.
- Tumor and cardiac tissues were histopathologically examined, and active caspase-3 was assessed via immunohistochemistry.
Main Results:
- SML significantly reduced tumor size and weight, both alone and in combination with DOX.
- SML treatment upregulated key apoptosis-related genes (Fas/FasL, TRAILR2/TRAIL, caspase-3) and downregulated Bcl-2.
- SML treatment enhanced DOX's anti-tumor activity and showed protective effects against DOX-induced cardiotoxicity.
Conclusions:
- Sesamol (SML) demonstrates anti-tumor properties by upregulating death receptors and promoting apoptosis in cancer cells.
- SML potentiates the anti-tumor efficacy of doxorubicin (DOX).
- Sesamol (SML) offers a promising strategy to enhance chemotherapy outcomes while mitigating cardiotoxic side effects.
