Antitumor Potential of Extracts Derived from Aerial Parts of Sigesbeckia orientalis L.: Cytotoxic Activities In Vitro and DMBA-induced Tumor Model in Swiss Mice

Vollständiger Abstract

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Background: Sigesbeckia orientalis L., a member of the Asteraceae family, is an annual herb traditionally used to treat various ailments, such as rheumatism and joint pain. Recent studies have increasingly focused on its potential pharmacological effects through various in vitro, in silico, and in vivo models. However, there are limited reports on its potential anti-tumor applications. Objective: This study aimed to investigate the cytotoxic effects of various extracts of S. orientalis on cancer cell lines and to evaluate the anti-tumor efficacy of the most active extract in a mouse tumor model. Moreover, a bioactivity-guided approach was used to isolate three bioactive compounds using a combination of chromatographic techniques. Methods: The cytotoxic activities of different S. orientalis extracts were assessed in vitro using the sulforhodamine B (SRB) assay against several cancer cell lines. The in vivo anti-tumor effects were evaluated in mice with tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA). Mice were orally administered the n-hexane extract (SOH) at doses of 100 and 300 mg/kg body weight per day. Immune responses were evaluated based on immune organ index, T-cell counts, and serum cytokine levels. Results: The SOH exhibited strong cytotoxicity, with IC50 values below 30 μg/mL across all tested cancer cell lines. In the DMBA-induced tumor model, mice treated with SOH showed reduced mortality up to the eighth week compared to the untreated control group. Additionally, SOH enhanced immune responses, as shown by increased immune organ indices, elevated T-cell counts, and higher serum levels of pro-inflammatory cytokines. Furthermore, three bioactive compounds were identified based on LC-MS and NMR data. By utilizing a combination of chromatographic techniques, three compounds were successfully isolated from this fraction, including ursolic acid (1), ferulic acid (2), and β-sitosterol (3). result: The n-hexane fraction (SOH) exhibited significant cytotoxicity against cancer cell lines, with IC50 values consistently below 30 μg/mL. In the DMBA-induced tumor model, SOH treatment reduced mortality rates up to the eighth week compared to the control group. Furthermore, SOH enhanced immune responses, as indicated by increased immune organ index, elevated T cell counts, and higher serum levels of pro-inflammatory cytokines. Conclusion: These findings suggest that S. orientalis exhibits promising anti-tumor potential through both cytotoxic and immune-stimulating mechanisms. The results support its potential as a complementary agent in phytomedicine-based cancer therapies.