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<p>Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, with few effective treatments for multidrug-resistant cases. Actinobacteria, particularly <i>Streptomyces</i> species, produce bioactive secondary metabolites with anticancer activity. However, the role of <i>Streptomyces violaceochromogenes</i> in CRC remains to be elucidated. This study aimed to characterize <i>S. violaceochromogenes</i> strain M12 and evaluate its cytotoxic, pro-apoptotic, cell cycle-modulating, and anti-migratory activities in CRC cells. Crude extracts were prepared via solvent extraction and identified using molecular biology techniques. Cytotoxicity against SW480 human colorectal cancer cells was assessed using the MTT assay. Apoptosis was evaluated using Annexin V-FITC/PI staining, caspase-3/7 activity, and quantitative real-time PCR analysis of apoptosis-related genes B-cell lymphoma 2 [<i>BCL2</i>], (BCL2-associated X [<i>BAX</i>], <i>CASPASE-8</i>, and <i>CASPASE-9</i>). Flow cytometry assessed cell cycle distribution. The antimigratory potential was determined using a scratch migration assay. The extract exhibited time-dependent cytotoxicity, with half-inhibitory concentration (IC₅₀) decreased from 248.5&#xa0;µg/mL at 24&#xa0;h to 64.52&#xa0;µg/mL at 96&#xa0;h (<i>p</i> &lt; 0.0001). Apoptosis analysis revealed significant upregulation of <i>BAX</i> (9.512 ± 1.122) and <i>CASPASE-9</i> (5.639 ± 1.038) (<i>p</i> &lt; 0.0001), with no notable changes in <i>BCL-2</i> (0.060 ± 0.015) or <i>CASPASE-8</i> (0.013 ± 0.002) expression, indicating apoptosis via the mitochondrial pathway. Cell cycle analysis revealed substantial redistribution of cells, from G1 (17.6%), S (8.31%), and G2/M (74.1%) in controls to 50.0%, 49.6%, and 0.3% after treatment, respectively (<i>p</i> &lt; 0.0001). The extract inhibited SW480 cell migration in a dose-dependent manner. Collectively, <i>S. violaceochromogenes</i> M12 produces cytotoxic metabolites with apoptosis-inducing, antimigratory, and cell cycle–arresting effects, highlighting its potential as an anticancer agent.</p> Graphical abstract <p></p>

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Anticancer Potential of Streptomyces sp. Strain M12: Apoptosis Induction and Anti-Migratory Effects in Colorectal Cancer Cells

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Ehsan Hasanzadeh,
  • Nasrin Motamed,
  • Ensieh Salehghamari,
  • Mahsa Fereidoni,
  • Maryam Taher,
  • Hanieh Jalali

摘要

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, with few effective treatments for multidrug-resistant cases. Actinobacteria, particularly Streptomyces species, produce bioactive secondary metabolites with anticancer activity. However, the role of Streptomyces violaceochromogenes in CRC remains to be elucidated. This study aimed to characterize S. violaceochromogenes strain M12 and evaluate its cytotoxic, pro-apoptotic, cell cycle-modulating, and anti-migratory activities in CRC cells. Crude extracts were prepared via solvent extraction and identified using molecular biology techniques. Cytotoxicity against SW480 human colorectal cancer cells was assessed using the MTT assay. Apoptosis was evaluated using Annexin V-FITC/PI staining, caspase-3/7 activity, and quantitative real-time PCR analysis of apoptosis-related genes B-cell lymphoma 2 [BCL2], (BCL2-associated X [BAX], CASPASE-8, and CASPASE-9). Flow cytometry assessed cell cycle distribution. The antimigratory potential was determined using a scratch migration assay. The extract exhibited time-dependent cytotoxicity, with half-inhibitory concentration (IC₅₀) decreased from 248.5 µg/mL at 24 h to 64.52 µg/mL at 96 h (p < 0.0001). Apoptosis analysis revealed significant upregulation of BAX (9.512 ± 1.122) and CASPASE-9 (5.639 ± 1.038) (p < 0.0001), with no notable changes in BCL-2 (0.060 ± 0.015) or CASPASE-8 (0.013 ± 0.002) expression, indicating apoptosis via the mitochondrial pathway. Cell cycle analysis revealed substantial redistribution of cells, from G1 (17.6%), S (8.31%), and G2/M (74.1%) in controls to 50.0%, 49.6%, and 0.3% after treatment, respectively (p < 0.0001). The extract inhibited SW480 cell migration in a dose-dependent manner. Collectively, S. violaceochromogenes M12 produces cytotoxic metabolites with apoptosis-inducing, antimigratory, and cell cycle–arresting effects, highlighting its potential as an anticancer agent.

Graphical abstract