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<p>The aim of the study was isolation of best probiotic from woman’s vagina and evaluate its anticancer properties and the toxicity of the secondary metabolites of the best isolated strain against the HT-29 cancer cells. Vaginal samples were collected from the cervix of healthy women in the north of Iran (Guilan). Molecular identification of the best lactobacillus isolate with probiotic properties was performed. Then, apoptotic and antiproliferative effects of the extract of the new isolate were evaluated compared to doxorubicin. Additionally, a docking study was conducted using USCF Chimera and AutoDock Vina software with 18 ligands and four target proteins, including <i>caspase</i>-3, <i>caspase</i>-8, <i>caspase</i>-9, and P<i>53</i>. Our results showed that the extract of <i>Lactobacillus crispatus</i> strain AE <i>(GenBank: PX247516</i>, IC50 of 1.54&#xa0;mg/ml) induced apoptosis and inhibited cancer cell growth. In addition, the extract of <i>Lactobacillus crispatus</i> in combination with doxorubicin chemotherapeutic drug had anticancer properties more than the probiotic or doxorubicin alone. Overexpression of <i>CASP</i>-3, <i>CASP</i>-8, <i>CASP</i>-9 and <i>P53</i> was found in combination therapy with the probiotic or doxorubicin in HT-29 cells by Q-RT-PCR Ligand No. 18 showed strong interactions with the target proteins 1JOX and 1YXQ, with affinities of -7.46&#xa0;kcal/mol and − 9.622&#xa0;kcal/mol, respectively. These results confirm a higher stability in docking interactions. Our analysis suggested that a new strain of <i>Lactobacillus crispatus</i> AE <i>(GenBank: PX247516</i>) from vigina as a probiotic can have anticancer effects. This is from the rare reports about this specie of genus Lactobacillus with strong anticancer activity against HT 29 cell lines. The best molecular docking results was detected in the secondary metabolite content encoded as 5,10-dideazatetrahydrofolic acid with an affinity of -9.622&#xa0;kcal/mol and formed 10 hydrogen bonds with the target protein 1JXQ, resulting in the most stable docking.</p>

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Overexpression of CASP-3, CASP-8, CASP-9 and P53 in HT-29 Cancer Cells after Co-Treatment of New Strain of Lactobacillus Crispatus Extract and Doxorobixin and Complementary Docking Study

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Azadehdokht Eftekhari Fumani,
  • Masoumeh Anvari,
  • Meysam Hasannejad-Bibalan,
  • Robabeh Sayyadi Kordabadi

摘要

The aim of the study was isolation of best probiotic from woman’s vagina and evaluate its anticancer properties and the toxicity of the secondary metabolites of the best isolated strain against the HT-29 cancer cells. Vaginal samples were collected from the cervix of healthy women in the north of Iran (Guilan). Molecular identification of the best lactobacillus isolate with probiotic properties was performed. Then, apoptotic and antiproliferative effects of the extract of the new isolate were evaluated compared to doxorubicin. Additionally, a docking study was conducted using USCF Chimera and AutoDock Vina software with 18 ligands and four target proteins, including caspase-3, caspase-8, caspase-9, and P53. Our results showed that the extract of Lactobacillus crispatus strain AE (GenBank: PX247516, IC50 of 1.54 mg/ml) induced apoptosis and inhibited cancer cell growth. In addition, the extract of Lactobacillus crispatus in combination with doxorubicin chemotherapeutic drug had anticancer properties more than the probiotic or doxorubicin alone. Overexpression of CASP-3, CASP-8, CASP-9 and P53 was found in combination therapy with the probiotic or doxorubicin in HT-29 cells by Q-RT-PCR Ligand No. 18 showed strong interactions with the target proteins 1JOX and 1YXQ, with affinities of -7.46 kcal/mol and − 9.622 kcal/mol, respectively. These results confirm a higher stability in docking interactions. Our analysis suggested that a new strain of Lactobacillus crispatus AE (GenBank: PX247516) from vigina as a probiotic can have anticancer effects. This is from the rare reports about this specie of genus Lactobacillus with strong anticancer activity against HT 29 cell lines. The best molecular docking results was detected in the secondary metabolite content encoded as 5,10-dideazatetrahydrofolic acid with an affinity of -9.622 kcal/mol and formed 10 hydrogen bonds with the target protein 1JXQ, resulting in the most stable docking.