Inhibition of Ras and STAT3 activity of 4-(tert-butyl)-N-carbamoylbenzamide as antiproliferative agent in HER2-expressing breast cancer cells

Kirtishanti, Aguslina and Siswodihardjo, Siswandono and Sudiana, I Ketut and Suprabawati, Desak G. A. and Dinaryanti, Aristika (2021) Inhibition of Ras and STAT3 activity of 4-(tert-butyl)-N-carbamoylbenzamide as antiproliferative agent in HER2-expressing breast cancer cells. Journal of Basic and Clinical Physiology and Pharmacology, 32 (2). pp. 363-371. ISSN 2191-0286

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	antiproliferative; breast cancer cells; HER2; Ras; STAT3; 4-(tert-butyl)-N-carbamoylbenzamide
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Pharmacy > Department of Pharmacy
Depositing User:	Ester Sri W. 196039
Date Deposited:	02 Sep 2021 08:23
Last Modified:	16 Jun 2023 05:33
URI:	http://repository.ubaya.ac.id/id/eprint/40154

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