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Review
. 2025 Jul 22;42(8):363.
doi: 10.1007/s12032-025-02792-4.

Natural bioactive compounds as notch signaling modulators: cutting-edge strategies for cancer therapy

Hasna Bouhenni #  1 , Mehrukh Zehravi #  2 , Faruk Reza  3 , Sherouk Hussein Sweilam  4   5 , Uppuluri Varuna Naga Venkata Arjun  6 , Thukani Sathanantham Shanmugarajan  6 , Ponnammal Ganesan Mahesh  6 , Akiladevi Durairaj  6 , Patibandla Jahnavi  7 , Venkatesan Natarajan  8 , Ali G Alkhathami  9 , Koula Doukani  10   11 , Talha Bin Emran  12
Affiliations
Review

Natural bioactive compounds as notch signaling modulators: cutting-edge strategies for cancer therapy

Hasna Bouhenni et al. Med Oncol. .

Abstract

Natural bioactive compounds have demonstrated potential in altering the Notch signaling system, a crucial regulator of cancer development. This review discusses the molecular interactions of various substances such as flavonoids, polyphenols, terpenoids, and alkaloids with ligands, receptors, and downstream effectors. Terpenoids like curcumin can combat Notch-mediated medication resistance, while flavonoids like quercetin prevent Notch receptor activation. Alkaloids that directly or indirectly modulate Notch signaling have anticancer effects. Preclinical and clinical investigations have demonstrated the effectiveness of several of these drugs, and several have progressed to clinical trials. The review emphasizes clinical trials to optimize the pharmacokinetics, safety, and therapeutic potential of natural medicines for cancer treatment. Natural bioactive substances targeting the Notch signaling system have the potential to develop cancer treatment. These treatments provide a potential alternative or supplement to current treatments due to their more targeted and less toxic approach to cancer cells. Natural bioactive compounds require further research to enhance pharmacokinetics, investigate processes, and conduct clinical trials.

Keywords: Cancer; Natural bioactive compounds; Notch signaling pathway; Therapeutic strategies.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable.

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