Toosendanin: upgrade of an old agent in cancer treatment

Abstract

Toosendanin (TSN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN’s toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras (PROTAC) technology and nanotechnology-based drug delivery systems (DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.

Keywords

Toosendanin / Cancer therapy / Hepatotoxicity / PROTAC / Nano-delivery systems

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Funding

National Natural Science Foundation of China(82322073)

National Natural Science Foundation of China(82304790)

National Natural Science Foundation of China(82173846)

China Postdoctoral Innovative Talent Support Program(BX20220213)

Shanghai Rising-Star Program(22QA1409100)

Oriental Scholars of Shanghai(TP2022081)

Jiangxi Province Thousand Talents Program(jxsq2023102168)

Young Talent Lifting Project of China Association of Chinese Medicine(No. CACM-(2021-QNRC2-A08))

Shanghai Science and Technology Innovation Action Plan(21S11902800)

Three-year Action Plan for Shanghai TCM Development and Inheritance Program(Nos. ZY (2021-2023)-0401)

Three-year Action Plan for Shanghai TCM Development and Inheritance Program(ZY (2021-2023)-0208)

Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202004)

CAMS Innovation Fund for Medical Sciences (CIFMS)(2023-I2M-3-009)

Shanghai Sailing Program(22YF1445000)

Shanghai Sailing Program(23YF1442600)

National Key R&D Program of China(2022YFC3502000)

Strategic Innovation Team of TCM Chemical Biology, Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(2023YZZ02)