Cyperus rotundus L. rhizome extract modulates immune system and induces apoptotic in 4T1-tumor bearing mice

Abstract

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.

In silico approach for predicting the bioactive compound of Cyperus rotundus to inhibit NF-kB and iNOS signaling pathways

“…The compounds demonstrated low toxicity to non-tumor cell line showed by lower Pa value compared to tumor cell line. A Previous study reported that C. rotundus extract was selective in killing murine breast cancer cell line (4T1) but not normal human fibroblast cell line (TIG-1) (Nafisah et al, 2023). Another study also demonstrated cytotoxic effect of C. rotundus against MCF-7 breast cancer cell line and affects the growth of vero cells (normal cell) (Simorangkir et al, 2019).…”

“…C. rotundus is a medicinal plant found in tropical and sub-tropical countries including Indonesia, China, India, Korea, Japan, and other countries (Nafisah et al, 2023;Xue et al, 2023). C. rotundus tuber ethanolic extract, specifically obtained from East Java, Indonesia, contained carboxylic acid, carboxylic ester, oligosaccharide, sulfur compound, amino acid, sesquiterpenes, amines, purines, and phenols.…”