Inhibition of Ras and STAT3 activity of 4-(tert-butyl)-N-carbamoylbenzamide as antiproliferative agent in HER2-expressing breast cancer cells
| Autor: | Aguslina Kirtishanti, Siswandono Siswodihardjo, I Ketut Sudiana, Aristika Dinaryanti, Desak G A Suprabawati |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Physiology medicine.drug_class Lapatinib Monoclonal antibody 03 medical and health sciences 0302 clinical medicine Breast cancer Drug Discovery medicine Cytotoxic T cell skin and connective tissue diseases STAT3 Pharmacology biology Chemistry General Medicine medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell STAT protein Cancer research biology.protein Janus kinase medicine.drug |
| Zdroj: | Journal of Basic and Clinical Physiology and Pharmacology. 32:363-371 |
| ISSN: | 2191-0286 |
| DOI: | 10.1515/jbcpp-2020-0508 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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