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<p>Triple-negative breast cancer (TNBC) remains one of the most aggressive and difficult-to-treat subtypes of breast cancer due to the lack of targeted therapies. This study investigates the anti-proliferative and anti-metastatic potential of fisetin (FIS) and its nanoformulations, nanotized fisetin (Nano-FIS) and FIS-loaded polymannose nanoparticles (FIS-PM NPs) in TNBC cells. Both Nano-FIS and FIS-PM NPs demonstrated significant, time- and dose-dependent cytotoxicity, with FIS-PM NPs showing the greatest inhibition of cell viability. Morphological assessments revealed pronounced apoptotic features, including cell shrinkage and rounding, particularly in nanoformulation-treated cells. In vitro wound healing assays confirmed that Nano-FIS and FIS-PM NPs markedly delayed cell migration compared to free FIS, indicating strong anti-metastatic properties. Western blot analysis further revealed that treatment with the nanoformulations downregulated pro-survival proteins NF-κB p65, Cyclin D1, and Bcl-2, while upregulating pro-apoptotic proteins Caspase-3 and Caspase-8, with FIS-PM NPs eliciting the most pronounced effects. RT-PCR analysis supported these findings by demonstrating significant downregulation of angiogenesis- and metastasis-related genes VEGF-A, VCAM1, MMP-9, and MMP-2 in nanoformulation-treated TNBC cells. Overall, the results suggest that FIS-based nanoformulations, particularly FIS-PM NPs, exhibit enhanced anti-cancer efficacy through the induction of apoptosis, inhibition of cell proliferation, migration, and angiogenesis, making them promising therapeutic candidates for TNBC treatment.</p>

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Exploration of mechanism of anticancer potential of fisetin nanoformulations: nanotized fisetin/fisetin loaded polymannose nanoparticles in the treatment of triple negative breast carcinoma

  • 期刊论文

  • 发表日期：

    2025年7月24日

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  • Neena Yadav,
  • Saswat Kumar Mohanty,
  • Sathyapriya Chandramohan,
  • V. K. Archana,
  • Kitlangki Suchiang,
  • Rukkumani Rajagopalan

摘要

Triple-negative breast cancer (TNBC) remains one of the most aggressive and difficult-to-treat subtypes of breast cancer due to the lack of targeted therapies. This study investigates the anti-proliferative and anti-metastatic potential of fisetin (FIS) and its nanoformulations, nanotized fisetin (Nano-FIS) and FIS-loaded polymannose nanoparticles (FIS-PM NPs) in TNBC cells. Both Nano-FIS and FIS-PM NPs demonstrated significant, time- and dose-dependent cytotoxicity, with FIS-PM NPs showing the greatest inhibition of cell viability. Morphological assessments revealed pronounced apoptotic features, including cell shrinkage and rounding, particularly in nanoformulation-treated cells. In vitro wound healing assays confirmed that Nano-FIS and FIS-PM NPs markedly delayed cell migration compared to free FIS, indicating strong anti-metastatic properties. Western blot analysis further revealed that treatment with the nanoformulations downregulated pro-survival proteins NF-κB p65, Cyclin D1, and Bcl-2, while upregulating pro-apoptotic proteins Caspase-3 and Caspase-8, with FIS-PM NPs eliciting the most pronounced effects. RT-PCR analysis supported these findings by demonstrating significant downregulation of angiogenesis- and metastasis-related genes VEGF-A, VCAM1, MMP-9, and MMP-2 in nanoformulation-treated TNBC cells. Overall, the results suggest that FIS-based nanoformulations, particularly FIS-PM NPs, exhibit enhanced anti-cancer efficacy through the induction of apoptosis, inhibition of cell proliferation, migration, and angiogenesis, making them promising therapeutic candidates for TNBC treatment.