Diterpenoids from Croton tonkinensis Gagnep as antitumor agents: A systematic review

Abstract

Introduction

Traditional Vietnamese medicine has a long history of using Kho sam (Croton tonkinensis Gagnep) in the treatment of various cancers. Kho sam is an ingredient in numerous remedies for salivary gland cancer, bronchial-lung cancer, colorectal cancer, and liver cancer. This systematic review aims to comprehensively evaluate the existing literature on diterpenoids isolated from C. tonkinensis and their antitumor activities.

Methods

The protocol for this systematic review was registered in PROSPERO (CRD42024579468). A search was performed on PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar on September 13, 2024. Two independent members conducted the steps of screening the article, scoring the risk of bias for the article, extracting and writing the results. Due to heterogeneity among the included studies, the results were narrative and no meta-analyses were conducted.

Results

From an initial retrieval of 500 articles, 11 met the inclusion criteria. These studies investigated thirty-seven different compounds, among which ent-kaurane diterpenoids with the 16-en-15-one functional group and 8,9-seco-ent-kaurane diterpenoids exhibited particularly cytotoxic effects. These effects were mediated through several molecular pathways, including protein kinase B, hypoxia-inducible factor-dependent transcription, heat shock protein, extracellular signal-regulating kinase 1/2, and AMP-activated protein kinase pathways.

Conclusions

Current literature highlights kongensin D, derived from C. tonkinensis, as the most promising candidate, demonstrating high anticancer activity and selectivity, along with in vivo antitumor potential and a favorable safety profile.