Globally, breast cancer is one of the most prevalent tumors in women and remains a major concern due to its high mortality rate. Although treatment options for this disease have evolved over the years, there are still many cases of recurrence and metastasis. In this con-text, considering the importance of evaluating less aggressive and more efficient therapeu-tic alternatives to aid in the treatment of breast cancer, the present study critically discuss-es the cytotoxic effects of diterpenoids isolated from Croton species (Euphorbiaceae). The articles were retrieved from different databases, from the first report published in 2005 to October 2025. A total of 115 diterpenoids were isolated from 15 Croton species and inves-tigated against different breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-468). These compounds mainly belong to the kaurane group (40%), followed by clerodane (14%), tigliane (12%), and abietane (10%). Of this total, only 25 compounds showed prom-ising results (IC50 = <10 µM). The mechanisms of action of the compounds crokokaugenoid A, kongensin A, kongensin D, ent-16β,17α-dihydroxykaurane, and lauicyclone A have been reported. These compounds likely act by inducing apoptosis, autophagy, cell cycle arrest, inhibition of cell migration and invasion, and DNA fragmentation in breast cancer cell lines. To date, no randomized clinical trials have been conducted using Croton diterpenoids for the treatment of breast cancer. Therefore, further studies on the modula-tion of the immune response by these natural products are essential to better understand their immunotherapeutic activity in the tumor microenvironment during breast cancer progression.
Bezerra et al. (Sat,) studied this question.