Natural Products Targeting Notch Signaling in Cancer: Mechanistic Insights and Food-Based Chemoprevention Potential

Within the intricate network of oncogenic pathways that orchestrate the insidious growth and spread of cancer, the Notch signaling pathway is well known for its multiple roles in regulating cell differentiation, influencing metastasis, cancer stem cells, angiogenesis, and immune evasion. This pathway can suppress tumors by promoting differentiation and inhibiting proliferation or, conversely, stimulate tumorigenesis by inhibiting apoptosis and maintaining stem cell properties. While current research proposes monoclonal antibodies as possible tools to regulate the Notch pathway, natural products offer a complementary approach, potentially providing a more nuanced and adaptable means of modulating this complex signaling cascade. With their long-standing history of serving as a mainstay in developing successful cancer chemotherapeutic agents, natural products possess immense potential against cancer. The objective of this article is to examine the potential of natural products as therapeutic agents that modulate the Notch pathway in cancer, specifically focusing on its sophisticated role in both promoting and suppressing tumorigenesis in preclinical and clinical settings while comprehensively covering the state-of-the-art research concerning Notch signaling in cancer. The article stands out by analyzing the preclinical and clinical scope of natural products targeting Notch signaling in cancer, especially mentioning the limitations in pharmacological and biopharmaceutical performance and highlighting the novelty of nanotechnology tools to overcome such limitations. It also highlights new aspects in the study of the Notch pathway.