Breast cancer is the most common cancer in women throughout the world, with new cases and deaths which continue to increase. Soursop leaves (Annona muricata L) have been used extensively in traditional medicine, including cancer. Acetogenin, alkaloids, and phenols contained in soursop leaves are known to have anti-cancer effects. Among them, acetogenin has the most dominant role and reported to have a cytotoxic effect on various cancer cell lines. This study aims to determine the cytotoxic activity of soursop leaf ethanol extract on T47D breast cancer cell line. Measurement of cytotoxic activity was carried out by the MTT method, and the viability percentage of T47D cells was calculated based on the absorbance values in the treatment, cell control, and media control groups of each replicate. The correlation between extract concentration and viability percentage of the T47D cell line was outlined in the regression equation to obtain the IC50 value. IC50 values of 109.91 ± 3.04 with R values 0.975 and R2 0.9508 obtained. R values close to 1 indicated a strong correlation between extract concentration and the percentage of living T47D cells. Meanwhile, the amount of R2 suggested that the level of AMEE had a 95.08% influence on the rate of cell viability, and the other 4.92% influenced by factors other than the AMEE dose. These results indicated that the ethanol extract of soursop leaves has a cytotoxic effect and has the potential to inhibit T47D cell proliferation in vitro.
Objectives
Human epidermal growth factor receptor type 2 (HER2)-expressing breast cancer patients indicate poor prognosis in disease progression. HER2 overexpression can increase activities of Ras-mitogen activated protein kinase (Ras-MAPK) pathway and Janus Kinase (JAK)-STAT3, increasing breast cancer cell proliferation as demonstrated by marker Ki67. Therapeutic options for HER2-expressing breast cancer are limited and have major side effects, so anticancer development as an antiproliferative is needed. From previous research, synthetic chemical 4-(tert-butyl)-N-carbamoylbenzamide (4TBCB) compound has cytotoxic activity in vitro on HER2-expressing breast cancer cells. This study wanted to determine the mechanism 4TBCB compound in inhibiting HER2 signaling through Rat Sarcoma (Ras) and signal transducer and activator of transcription 3 (STAT3) pathway in HER2-expressing breast cancer cells.
Methods
Breast cancer cells were isolated from the biopsy tissue of breast cancer patients. The isolated cells were cultured and given 4TBCB test compound with three concentrations (0.305, 0.61, and 1.22 mM) and lapatinib 0.05 mM as a comparison compound. Cancer cell cultures were stained with monoclonal antibodies phosphorylated HER2 (pHER2), phosphorylated Ras (pRas), phosphorylated STAT3 (pSTAT3), and Ki67. The expression of pHER2, pRas, pSTAT3, and Ki67 proteins was observed using the immunofluorescence method and the results were compared with control cells, namely cancer cells that were not given 4TBCB and lapatinib but stained with monoclonal antibodies.
Results
4TBCB compounds (0.61 and 1.22 mM) and lapatinib can reduce pHER2, pRas, pSTAT3, and Ki67 expressions compared to control cells.
Conclusions
4TBCB compounds (0.61 and 1.22 mM) can reduce pHER2, pRas, pSTAT3, Ki67 expressions and predicted to inhibit HER2 signaling through the Ras and STAT3 pathways in HER2-expressing breast cancer cells.
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