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<p>Gastric cancer is a leading cause of cancer-related mortality worldwide, largely due to its late diagnosis, aggressive progression, and the adverse effects of current treatment options. There is a growing interest in identifying natural, less toxic alternatives, with plant-derived compounds offering promising therapeutic potential. Resveratrol, a polyphenol found in red grapes, has demonstrated notable anticancer effects by modulating several cellular pathways involved in tumor development. This study aimed to evaluate the anticancer effects of resveratrol and red grape extract on AGS human gastric adenocarcinoma cells, with a focus on cell viability, apoptosis, cell cycle dynamics, and gene expression. Red grape extract was prepared, and resveratrol solubility was systematically assessed in a panel of pharmaceutical excipients. AGS human gastric cancer cells and corresponding normal fibroblasts were cultured and subjected to controlled mechanical injury prior to treatment. Cytotoxicity of the extract and resveratrol was evaluated using the MTT assay to determine effects on cell viability. Apoptosis was quantified by flow cytometry using the Annexin V–FITC/propidium iodide (PI) assay. The expression levels of apoptosis-related genes were analyzed by quantitative real-time PCR (qRT-PCR). In addition, total antioxidant capacity (TAC) was measured to assess treatment-induced oxidative alterations. Using MTT assays, both resveratrol and red grape extract showed dose- and time-dependent inhibition of AGS cell proliferation, with resveratrol displaying a stronger effect (IC₅₀: 7.812&#xa0;µg/mL) compared to red grape extract (IC₅₀: 31.25&#xa0;µg/mL) at 48 and 72&#xa0;h. In contrast, neither compound significantly affected the viability of normal HGF1-PI 1 fibroblast cells. Flow cytometry revealed that resveratrol induced higher levels of apoptosis (53.72%) in AGS cells than red grape extract (41.4%), with selective action favoring cancer cells over normal cells. Gene expression analysis via RT-qPCR demonstrated that resveratrol significantly upregulated pro-apoptotic gene MCC and anti-apoptotic ERBB2 gene, while downregulating anti-apoptotic genes CCND1, MICAL2, and PAK1 in AGS cells. No significant gene modulation occurred in normal cells. Additionally, resveratrol markedly decreased the total antioxidant capacity (TAC) in AGS cells, suggesting a pro-oxidant mechanism of action, while TAC in normal cells remained unchanged. In conclusion, resveratrol exhibits potent and selective anticancer effects on gastric cancer cells, including apoptosis induction, cell cycle arrest, and gene modulation, with minimal cytotoxicity toward normal fibroblasts. These findings underscore resveratrol’s potential as a promising natural agent in gastric cancer therapy.</p>

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Anticancer effects of red grape, and resveratrol on AGS gastric cancer cell line and investigation of related gene expression

  • 期刊论文

  • 发表日期：

    2026年1月6日

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  • Maedeh Shirazi,
  • Kahin Shahanipour,
  • Ramesh Monajemi,
  • Nasrin Yazdanpanahi

摘要

Gastric cancer is a leading cause of cancer-related mortality worldwide, largely due to its late diagnosis, aggressive progression, and the adverse effects of current treatment options. There is a growing interest in identifying natural, less toxic alternatives, with plant-derived compounds offering promising therapeutic potential. Resveratrol, a polyphenol found in red grapes, has demonstrated notable anticancer effects by modulating several cellular pathways involved in tumor development. This study aimed to evaluate the anticancer effects of resveratrol and red grape extract on AGS human gastric adenocarcinoma cells, with a focus on cell viability, apoptosis, cell cycle dynamics, and gene expression. Red grape extract was prepared, and resveratrol solubility was systematically assessed in a panel of pharmaceutical excipients. AGS human gastric cancer cells and corresponding normal fibroblasts were cultured and subjected to controlled mechanical injury prior to treatment. Cytotoxicity of the extract and resveratrol was evaluated using the MTT assay to determine effects on cell viability. Apoptosis was quantified by flow cytometry using the Annexin V–FITC/propidium iodide (PI) assay. The expression levels of apoptosis-related genes were analyzed by quantitative real-time PCR (qRT-PCR). In addition, total antioxidant capacity (TAC) was measured to assess treatment-induced oxidative alterations. Using MTT assays, both resveratrol and red grape extract showed dose- and time-dependent inhibition of AGS cell proliferation, with resveratrol displaying a stronger effect (IC₅₀: 7.812 µg/mL) compared to red grape extract (IC₅₀: 31.25 µg/mL) at 48 and 72 h. In contrast, neither compound significantly affected the viability of normal HGF1-PI 1 fibroblast cells. Flow cytometry revealed that resveratrol induced higher levels of apoptosis (53.72%) in AGS cells than red grape extract (41.4%), with selective action favoring cancer cells over normal cells. Gene expression analysis via RT-qPCR demonstrated that resveratrol significantly upregulated pro-apoptotic gene MCC and anti-apoptotic ERBB2 gene, while downregulating anti-apoptotic genes CCND1, MICAL2, and PAK1 in AGS cells. No significant gene modulation occurred in normal cells. Additionally, resveratrol markedly decreased the total antioxidant capacity (TAC) in AGS cells, suggesting a pro-oxidant mechanism of action, while TAC in normal cells remained unchanged. In conclusion, resveratrol exhibits potent and selective anticancer effects on gastric cancer cells, including apoptosis induction, cell cycle arrest, and gene modulation, with minimal cytotoxicity toward normal fibroblasts. These findings underscore resveratrol’s potential as a promising natural agent in gastric cancer therapy.