Abstract
OBJECTIVE: To evaluate the anticancer potential of Acteoside and Plantamajoside using MCF-7 cancer cell line. METHODS: In this study, the half-maximal inhibitory concentration (IC50) values of Acteoside and Plantamajoside were investigated using the Sulforhodamine B (SRB) assay. The IC50 values of both compounds were utilized in the clonogenic and scratch wound assays to assess cell survival and migration, respectively. The cells with treatments were also analyzed using the Caspase 3/7 assay to determine their capability to induce cell apoptosis. Network Pharmacology was used to evaluate their probable protein targets and pharmacological mechanisms. RESULTS: Acteoside and Plantamajoside exhibited cytotoxic activity against the MCF-7 cancer cell line in vitro, with IC50 values of 134.83 μg/mL and 225.10 μg/mL, respectively. This was further supported by clonogenic assay, which showed a difference in colony formation following treatment with ACT and PMS, compared to the negative control. Specifically, ACT resulted in the formation of only 39.7% of colonies, whereas PMS formed 51.12% of colonies, indicating that these compounds impaired the cells' ability to proliferate and form colonies. Moreover, these compounds were also able to inhibit cell migration as a reduction in the migration area of the MCF-7 cell line was observed. An increase in the percentage of apoptotic cells was also noted post-treatment, which correlated with elevated Caspase 3/7 activity, indicating that these compounds may effectively induce cellular apoptosis. In silico predictions demonstrated that the compounds' anticancer effect may be attributed to their interactions with TLR, PI3K, and STAT-all are implicated in the PD-1 checkpoint pathway and PD-L1 expression in cancer. CONCLUSION: Both Acteoside and Plantamajoside have demonstrated promising anticancer properties by inhibiting the growth and metastasis of MCF-7 cancer cell line. These compounds induce apoptosis, modulate the PD-1 checkpoint pathway, and influence PD-L1 expression, which may indicate possible molecular mechanisms for their anticancer effects.