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<p>Medicinal plants have long held therapeutic value in traditional medicine, though their underlying biological mechanisms are often underexplored. The tubers of <i>Cyperus rotundus</i> are rich in bioactive flavonoids, and previous studies confirm their diverse phytochemical composition. We hypothesize that the total oligomeric flavonoid (TOF) fraction from <i>C. rotundus</i> exerts selective anticancer effects via a synthetic lethality-like mechanism—targeting malignant cells while sparing normal ones. This study investigated TOF’s cytotoxic and mechanistic effects on six cancer cell lines: human glioblastoma (AMGM), mouse mammary adenocarcinoma (AMN3), breast cancer (MCF7 and AMJ13), ovarian cancer (SKOV3), cervical carcinoma (HeLa), and rhabdomyosarcoma (RD). Two normal cell lines—rat embryo fibroblasts (REF) and African green monkey kidney cells (Vero)—served as controls. TOF was applied at concentrations of 50–500&#xa0;µg/mL over 24, 48, and 72&#xa0;h. Radical scavenging capacity was assessed via DPPH assay, with 100, 200, and 300&#xa0;µg/mL TOF reducing DPPH by 59.56%, 78.9%, and 93.55% relative to ascorbic acid, confirming strong free radical scavenging activity. MTT assays revealed antiproliferative effects with IC<sub>50</sub> values ranging from 253.29&#xa0;µg/mL (AMJ13 at 72&#xa0;h) to 8620.68&#xa0;µg/mL (VERO at 24&#xa0;h). Cytopathological changes were visualized using crystal violet staining. Apoptosis was confirmed by acridine orange/propidium iodide dual staining, mitochondrial membrane potential disruption, DNA fragmentation, and comet assay—all indicating selective apoptosis in cancer cells while preserving normal cell integrity. Total antioxidant status (TAS) analysis showed increased activity in extracellular fractions post-treatment and reduced activity intracellularly, with the most significant shifts observed in AMJ13 and HeLa cells. Overall, TOF demonstrated potent anticancer properties through apoptosis induction and oxidative stress modulation. These findings support its potential as a selective, plant-derived therapeutic candidate and justify further investigation toward safer, targeted cancer treatments.</p>

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Oligomeric flavonoids from Cyperus rotundus tubers suppress growth, induce apoptosis, and boost antioxidant defense in multiple cancer cell lines

  • 期刊论文

  • 发表日期：

    2025年9月27日

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  • Amer Talib Tawfeeq,
  • Zaynab Saad Abdulgany,
  • Noah Abdulkhder Mahmood,
  • Esraa Jaafar Saheb,
  • Mohammed Saleh Abbas

摘要

Medicinal plants have long held therapeutic value in traditional medicine, though their underlying biological mechanisms are often underexplored. The tubers of Cyperus rotundus are rich in bioactive flavonoids, and previous studies confirm their diverse phytochemical composition. We hypothesize that the total oligomeric flavonoid (TOF) fraction from C. rotundus exerts selective anticancer effects via a synthetic lethality-like mechanism—targeting malignant cells while sparing normal ones. This study investigated TOF’s cytotoxic and mechanistic effects on six cancer cell lines: human glioblastoma (AMGM), mouse mammary adenocarcinoma (AMN3), breast cancer (MCF7 and AMJ13), ovarian cancer (SKOV3), cervical carcinoma (HeLa), and rhabdomyosarcoma (RD). Two normal cell lines—rat embryo fibroblasts (REF) and African green monkey kidney cells (Vero)—served as controls. TOF was applied at concentrations of 50–500 µg/mL over 24, 48, and 72 h. Radical scavenging capacity was assessed via DPPH assay, with 100, 200, and 300 µg/mL TOF reducing DPPH by 59.56%, 78.9%, and 93.55% relative to ascorbic acid, confirming strong free radical scavenging activity. MTT assays revealed antiproliferative effects with IC50 values ranging from 253.29 µg/mL (AMJ13 at 72 h) to 8620.68 µg/mL (VERO at 24 h). Cytopathological changes were visualized using crystal violet staining. Apoptosis was confirmed by acridine orange/propidium iodide dual staining, mitochondrial membrane potential disruption, DNA fragmentation, and comet assay—all indicating selective apoptosis in cancer cells while preserving normal cell integrity. Total antioxidant status (TAS) analysis showed increased activity in extracellular fractions post-treatment and reduced activity intracellularly, with the most significant shifts observed in AMJ13 and HeLa cells. Overall, TOF demonstrated potent anticancer properties through apoptosis induction and oxidative stress modulation. These findings support its potential as a selective, plant-derived therapeutic candidate and justify further investigation toward safer, targeted cancer treatments.