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<p>Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Emerging therapies focus on probiotics and herbal compounds as adjuncts to conventional treatments because of their ability to enhance apoptosis. The anticancer effects of <i>Lactobacillus brevis</i>, isolated from traditional Iranian yogurt, and ginger were investigated in the HT-29 cell culture. <i>L. brevis</i> was isolated from a local dairy using MRS media, and identification was confirmed through morphology, biochemical characteristics, and phylogenetic analysis by 16S rRNA gene sequencing. An ethanolic extract of ginger was prepared by maceration. Anticancer evaluations included MTT assays for cell viability, apoptosis detection by flow cytometry, comparison of <i>BAX</i>, <i>BCL</i>-2, and <i>CASP3</i> mRNA levels by qRT-PCR, and GC–MS analysis to determine the components of the <i>L. brevis</i> extract (LBE). The experimental data showed a decrease in cell viability, with the IC<sub>50</sub> concentrations for LBE at 2.015&#xa0;mg/ml significantly reducing HT-29 cell viability (<i>P</i> &lt; 0.0001). It exhibited a much stronger cytotoxic effect than ginger extract, which has an IC<sub>50</sub> of 700.7&#xa0;µg/ml; however, the reduction compared to the control was not statistically significant. LBE also significantly increased apoptotic cells from 1.74 to 49.53%. Gene expression analysis indicated downregulation of <i>BCL</i>-2 and <i>CASP3</i> genes and upregulation of <i>BAX</i> (LBE 1.38; ginger 1.74-fold; <i>P</i> &lt; 0.001). A significant correlation was observed between CASP3 and BCL-2 gene expression with r = 0.985 (<i>P</i> &lt; 0.0001). The GC–MS analysis identified bioactive metabolites, including alkanes and heterocyclic compounds. The data presented here suggest that <i>L. brevis</i> may be a viable probiotic candidate for inducing apoptosis in CRC cells.</p>

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Enhanced modulation of BAX, BCL-2, and CASP3 gene expression by Levilactobacillus brevis from traditional yogurt and ginger to induce apoptosis in HT-29 cell line

  • 期刊论文

  • 发表日期：

    2026年1月31日

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  • Fatemeh Erfani Jahed Noghan,
  • Masoumeh Anvari,
  • Hadi Habibollahi,
  • Mahdi Shahriarinour

摘要

Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Emerging therapies focus on probiotics and herbal compounds as adjuncts to conventional treatments because of their ability to enhance apoptosis. The anticancer effects of Lactobacillus brevis, isolated from traditional Iranian yogurt, and ginger were investigated in the HT-29 cell culture. L. brevis was isolated from a local dairy using MRS media, and identification was confirmed through morphology, biochemical characteristics, and phylogenetic analysis by 16S rRNA gene sequencing. An ethanolic extract of ginger was prepared by maceration. Anticancer evaluations included MTT assays for cell viability, apoptosis detection by flow cytometry, comparison of BAX, BCL-2, and CASP3 mRNA levels by qRT-PCR, and GC–MS analysis to determine the components of the L. brevis extract (LBE). The experimental data showed a decrease in cell viability, with the IC50 concentrations for LBE at 2.015 mg/ml significantly reducing HT-29 cell viability (P < 0.0001). It exhibited a much stronger cytotoxic effect than ginger extract, which has an IC50 of 700.7 µg/ml; however, the reduction compared to the control was not statistically significant. LBE also significantly increased apoptotic cells from 1.74 to 49.53%. Gene expression analysis indicated downregulation of BCL-2 and CASP3 genes and upregulation of BAX (LBE 1.38; ginger 1.74-fold; P < 0.001). A significant correlation was observed between CASP3 and BCL-2 gene expression with r = 0.985 (P < 0.0001). The GC–MS analysis identified bioactive metabolites, including alkanes and heterocyclic compounds. The data presented here suggest that L. brevis may be a viable probiotic candidate for inducing apoptosis in CRC cells.