Context: The development of apoptotic agent from natural plant products may have a beneficial effect as a promising candidate for cancer therapy. The study about the efficacy of Phaleria macrocarpa leaves on breast cancer is still limited. Aims: To elucidate the molecular mechanisms underlying the anti-breast cancer activity of P. macrocarpa leaves extract by in silico analysis. Methods: The compounds of the ethanol extract of P. macrocarpa were identified by Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS) analysis. Fourteen bioactive compounds of P. macrocarpa leaf were analyzed to determine the biological activity using Prediction of Activity Spectra for Substances (PASS) server. The network analysis was analyzed using STRING (https://string-db.org/). Twelve selected compounds were docked with several protein targets, including caspase 3, Bax and Bcl-2. Molecular docking was done by Pyrx 0.8 software and visualized by Discovery Studio software. The pharmacological properties of investigated bioactive compounds were analyzed using the SwissADME web server. Results: The twelve from fourteen bioactive compounds of P. macrocarpa leaf have anticancer properties and might be expected to involve in p53 and PI3K/Akt signaling pathways related to cancer. The molecular docking result showed that sesamin from the lignans group has the best binding affinity to caspase-3 and Bax. Meanwhile, corymboside from the flavonoid group has the best binding affinity to Bcl-2. Conclusions: The bioactive compounds of P. macrocarpa leaves extract might potentially modulate apoptosis and cell growth. Further research should be performed to validate the activity of P. macrocarpa bioactive compounds for target cancer development.

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Background: The carcinogenic substance 7,12-Dimethylbenz[a]anthracene (DMBA) was commonly used to induce tumor formation in rodents. The development of tumor may trigger higher expression of pro-inflammatory cytokines, which in turn supports tumor progression. In this study, we examined the efficacy of Cyperus rotundus extract (CRE) that was reported to have anti-inflammatory properties. We focused on investigating the levels of activated T lymphocytes and the pro-inflammatory cytokines expressed by macrophages. Methods: Female BALB/c were injected with DMBA subcutaneously. The DMBA exposed mice were given CRE orally in three different doses; 63.33, 158.4, and 316.8 mg/kg. After 14 days, the levels of activated T lymphocytes and pro-inflammatory cytokines were analyzed using flow cytometry. Graphical analysis was done with FlowJo v10 and followed by statistical analysis. Results: The treatment of CRE reduced the population of CD4 and CD8 T cells. The number of activated CD4 and CD8 T cells were also significantly suppressed. The population of macrophages marked by CD11b cells was significantly reduced. Finally, the CRE treatment suppressed the levels of TNF-α, IFN-γ, IL-1β, and IL-6 expressed by macrophages. Conclusion: Our findings suggest that CRE could be a potential agent useful in therapeutic approaches for curing the disease caused by aberrant cells.

Context: Triple-negative breast cancer (TNBC) is a type of breast cancer with the highest aggressiveness and malignancy characteristics. Aims: To evaluate the possible anticancer potential of Cyperus rotundus rhizome extract (CRE) against 4T1-tumor-bearing mice. Methods: C. rotundus rhizome was extracted using maceration methods with ethanol. C. rotundus extract (CRE) was then determined the total phenolic (TPC) and flavonoid content (TFC) using colorimetric analysis. The cytotoxic activity of CRE against 4T1 cells was carried out operating WST-1 assay, and the IC50 value was then used for in vivo study. The 4T1-tumor-bearing mice were treated with CRE at 72.5, 145, and 290 mg/kg body weight (BW) for two weeks or treated with cisplatin once a week for two weeks (4 mg/kg BW). The analysis of IL-2 cytokines production and the activation of CD4 and CD8 T cells was assessed using flow cytometry analysis. Histopathological analysis with hematoxylin and eosin (HE) staining was applied to determine the outcome of CRE on breast cancer tissue. Results: CRE indicated a higher TPC (76.97 mg GAE/g) value than TFC (29.37 mg QE/g). This study demonstrated a significant reduction of IL-2 cytokines and CD4 T cell activation in treated groups than in the cancer group (p<0.05) and showed a good prognosis, further confirmed by histopathological data. The breast tissue of 4T1-tumor-bearing mice in treated groups showed apoptotic cells compared to the cancer group, which has more viable cells. Conclusions: The high phenolic content in CRE can modulate mice's immune systems and induce cancer cell apoptosis.

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