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Published on: September 13, 2024
Caspase-dependent mitochondrial apoptotic pathway is involved in astilbin-mediated cytotoxicity in breast carcinoma
Xiaoqi Sun1, Hong Zhang1, Yingyu Zhang1
1Faculty of Clinical Medicine, Changchun Medical College, Changchun, Jilin 130031, P.R. China.
Abstract:
Astilbin exhibits several pharmacological activities, including hypoglycemic, anti-oxidant and anti-inflammatory properties. The aim of the present study was to investigate the pro-apoptotic activities of astilbin on breast cancer in cells and mice. It was demonstrated that astilbin significantly reduced the cell viability, increased the cell apoptosis rate, suppressed the migration ability, caused the dissipation of the mitochondrial membrane potential and induced the overaccumulation of intracellular reactive oxygen species in MCF-7 and MDA-MB-231 cells after 12 or 24 h of exposure. Data obtained from western blotting suggested that astilbin suppressed the expression levels of B-cell lymphoma 2 (Bcl-2), while it increased the expression levels of cleaved caspase-3, -8 and -9, and Bcl-2-associated X protein in breast carcinoma cells. Furthermore, astilbin inhibited the growth of MCF-7-xenografted tumors in nude mice without influencing their bodyweights or organ (liver, spleen and kidney) functions. Additionally, astilbin enhanced the expression of pro-apoptotic proteins and suppressed the expression of anti-apoptotic proteins in tumor tissues. All these results revealed that astilbin exhibits pro-apoptotic properties in breast carcinoma cells via modulation of the caspase-dependent pathway, which highlights the feasibility of astilbin as a candidate agent for breast cancer treatment.
Insights
Astilbin demonstrates significant potential as a breast cancer treatment by inducing cancer cell death and inhibiting tumor growth in mice. This natural compound effectively targets apoptosis pathways, offering a promising therapeutic avenue.
Area of Science:
- Pharmacology
- Oncology
- Cell Biology
Background:
- Astilbin is known for hypoglycemic, antioxidant, and anti-inflammatory effects.
- Breast cancer remains a leading cause of mortality worldwide, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the pro-apoptotic effects of astilbin on breast cancer cells and in vivo tumor models.
- To elucidate the molecular mechanisms underlying astilbin's anti-cancer activity.
Main Methods:
- In vitro studies using MCF-7 and MDA-MB-231 breast cancer cell lines.
- Western blotting to analyze apoptosis-related protein expression.
- In vivo xenograft tumor model in nude mice.
Main Results:
- Astilbin reduced cancer cell viability, increased apoptosis, and suppressed migration.
- It induced mitochondrial membrane potential dissipation and reactive oxygen species accumulation.
- Astilbin modulated the caspase-dependent pathway by downregulating Bcl-2 and upregulating cleaved caspases and Bax.
- Tumor growth inhibition was observed in vivo without adverse effects on body weight or organ function.
Conclusions:
- Astilbin exhibits potent pro-apoptotic properties against breast cancer cells.
- Its mechanism involves the caspase-dependent pathway and modulation of key apoptotic proteins.
- Astilbin shows promise as a potential therapeutic agent for breast cancer treatment.
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