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Toosendanin: upgrade of an old agent in cancer treatment

Shuwei Li1, Qingyi Xiong1, Yiwen Shen1

  • 1Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital; Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Chinese Journal of Natural Medicines
|October 20, 2024
PubMed

Insights

Toosendanin (TSN), a natural compound, shows promise for cancer treatment by inhibiting tumor growth and spread. However, its toxicity necessitates advanced strategies like PROTAC and nanotechnology for safer, more effective cancer therapy.

Area of Science:

  • Natural Product Chemistry
  • Pharmacology
  • Oncology

Background:

  • Toosendanin (TSN), a tetracyclic triterpenoid from Melia species, is explored for anticancer properties.
  • Historically used as a pesticide, TSN exhibits potential in cancer treatment through various mechanisms.
  • Significant hepatotoxicity of TSN poses a major challenge for its clinical application.

Purpose of the Study:

  • To review the dual role of TSN in cancer therapy, balancing efficacy and toxicity.
  • To explore novel therapeutic strategies for TSN, including PROTAC and nanotechnology.
  • To assess methods for enhancing TSN's therapeutic index in cancer treatment.

Main Methods:

  • Literature review of TSN's anticancer mechanisms and toxicological profile.
  • Analysis of emerging therapeutic strategies incorporating TSN.
  • Evaluation of Proteolysis-targeting chimeras (PROTAC) and drug delivery systems (DDS) for TSN delivery.

Main Results:

  • TSN demonstrates anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and angiogenesis.
  • TSN exhibits significant hepatotoxicity, limiting its direct therapeutic use.
  • PROTAC technology and nanotechnology-based DDS show potential to improve TSN's efficacy and reduce toxicity.

Conclusions:

  • TSN possesses considerable anticancer potential but requires careful management of its toxicity.
  • Novel strategies like PROTAC and DDS are crucial for overcoming TSN's limitations.
  • Balancing anticancer efficacy with reduced toxicity is key for successful TSN-based cancer therapeutics.
Keywords:
Cancer therapyHepatotoxicityNano-delivery systemsPROTACToosendanin

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