Scholarlink

<p><i>Erythrophleum suaveolens</i> stem bark (ESSB) exhibits anti-cancer activity against MCF-7 breast cancer cells, but its genotoxic mechanisms remain unclear. This study presented an exploratory investigation of the cytotoxic and genotoxic potential of ESSB methanol extracts and their flavonoids and alkaloid fractions in MCF-7 breast cancer cells, using a combination of in vitro biochemical assays, phytochemical profiling, and in silico bioinformatics. MCF-7 cells were exposed to ESSB extracts and fractions. Cytotoxicity and genotoxicity were evaluated using cell viability, DNA fragmentation and alkaline comet assays. Mitochondrial function was assessed via mitochondrial membrane permeability transition (MMPT) and succinate dehydrogenase activity in isolated rat liver mitochondria. Additionally, in silico studies were conducted to identify molecular targets and signaling pathways modulated by the methanol extracts, flavonoids and alkaloid phytoconstituents of ESSB identified by GC-MS in this study. ESSB methanol extracts I, II and flavonoid fraction reduced cell viability in MCF-7 cells with an IC<sub>50</sub> values of 78.12, 82, and 86.53&#xa0;µg/mL, respectively. After 72&#xa0;h, ESSB-treated MCF-7 cells showed a significant (<i>p</i> &lt; 0.05) increase in DNA fragmentation and comet tail DNA percentages (flavonoids induced a 1.21-fold increase in comet tail length). Flavonoids reduced mitochondrial swelling in a concentration-dependent manner, whereas ESSB extracts and alkaloids induced mitochondrial swelling at all concentrations. ESSB extracts enhanced succinate dehydrogenase activity, while both flavonoids and alkaloid fractions decreased it. In silico analysis predicted that ESSB extracts and fractions modulate key cancer-related pathways—including PI3K-Akt, HIF-1, TNF, MAPK, and NF-κB—and regulate apoptosis, autophagy, and cell cycle processes. Genotoxic effects of ESSB extracts and alkaloids were speculated to be mediated through mitochondrial DNA damage and apoptosis, while flavonoids putatively acted via non-mitochondrial mechanisms involving nuclear damage, proteolysis, and vesicular trafficking. These findings suggest the therapeutic potential of ESSB bioactives as multi-target agents in breast cancer treatment, further validation through well-structured in vitro and in vivo mechanistic studies is required.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genotoxic mechanisms of Erythrophleum suaveolens stem bark extracts and fractions in MCF-7 breast cancer cells via mitochondrial and non-mitochondrial pathways

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月26日

查看全文
  • Rahmat A. Adisa,
  • Lateef A. Sulaimon,
  • Kolawole Ekoh,
  • Kolawole Oluwole-Banjo,
  • Olumide Adebesin,
  • Adeleke T. Ogunnaike,
  • Victor C. Obioma,
  • Oluwaseun O. Taofeek,
  • Lukman O. Afolabi,
  • Sani A. Hamza

摘要

Erythrophleum suaveolens stem bark (ESSB) exhibits anti-cancer activity against MCF-7 breast cancer cells, but its genotoxic mechanisms remain unclear. This study presented an exploratory investigation of the cytotoxic and genotoxic potential of ESSB methanol extracts and their flavonoids and alkaloid fractions in MCF-7 breast cancer cells, using a combination of in vitro biochemical assays, phytochemical profiling, and in silico bioinformatics. MCF-7 cells were exposed to ESSB extracts and fractions. Cytotoxicity and genotoxicity were evaluated using cell viability, DNA fragmentation and alkaline comet assays. Mitochondrial function was assessed via mitochondrial membrane permeability transition (MMPT) and succinate dehydrogenase activity in isolated rat liver mitochondria. Additionally, in silico studies were conducted to identify molecular targets and signaling pathways modulated by the methanol extracts, flavonoids and alkaloid phytoconstituents of ESSB identified by GC-MS in this study. ESSB methanol extracts I, II and flavonoid fraction reduced cell viability in MCF-7 cells with an IC50 values of 78.12, 82, and 86.53 µg/mL, respectively. After 72 h, ESSB-treated MCF-7 cells showed a significant (p < 0.05) increase in DNA fragmentation and comet tail DNA percentages (flavonoids induced a 1.21-fold increase in comet tail length). Flavonoids reduced mitochondrial swelling in a concentration-dependent manner, whereas ESSB extracts and alkaloids induced mitochondrial swelling at all concentrations. ESSB extracts enhanced succinate dehydrogenase activity, while both flavonoids and alkaloid fractions decreased it. In silico analysis predicted that ESSB extracts and fractions modulate key cancer-related pathways—including PI3K-Akt, HIF-1, TNF, MAPK, and NF-κB—and regulate apoptosis, autophagy, and cell cycle processes. Genotoxic effects of ESSB extracts and alkaloids were speculated to be mediated through mitochondrial DNA damage and apoptosis, while flavonoids putatively acted via non-mitochondrial mechanisms involving nuclear damage, proteolysis, and vesicular trafficking. These findings suggest the therapeutic potential of ESSB bioactives as multi-target agents in breast cancer treatment, further validation through well-structured in vitro and in vivo mechanistic studies is required.