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Year : 2020  |  Volume : 11  |  Issue : 4  |  Page : 163-168

Anticancer evaluation of N-benzoyl-3-allylthiourea as potential antibreast cancer agent through enhances HER-2 expression

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60155, Indonesia
2 Department of Pharmaceutical Chemistry; Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia

Correspondence Address:
Dr. Tri Widiandani
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60155; Gedung Nanizar Zaman Joenoes. Kampus C UNAIR, Jl Mulyorejo, Surabaya
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/japtr.JAPTR_77_20

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Breast cancer with HER-2 overexpression is sensitive to drugs which target the receptor or its kinase activity. Although the anti-HER-2 therapies commonly used have improved patient outcome, resistance usually occurs. In this present study, we investigated a modification of the chemical structure of allylthiourea derivatives in order to enhance the cytotoxicity effect on breast cancer cells with HER-2 overexpression. The aim of this research was to predict the absorption, distribution, metabolism, excretion, and toxicity by in silico study and to explore the effect N-benzoyl-3-allylthiourea (BATU) on MCF-7 cell line with overexpressing of HER-2 using MTT assay and western blot. The result showed that the cytotoxicity effects of BATU on MCF-7/HER-2 cell line (IC50value 0.64 mM) were higher than on MCF-7 cell lines (IC50value 1.47 mM). In addition, the cytotoxic effects of BATU on MCF-7 and MCF-7/HER-2 were higher than allylthiourea as a lead compound (IC50value 5.22 and 3.17 mM). The results also confirmed that the BATU compound has the ability to effectively enhance its cytotoxicity against MCF-7/HER-2 through enhanced HER-2 expression and inhibition of nuclear factor kappa B (NF-kB) activation. Above all, the BATU compound is effective in increasing HER-2 expression and inactivating NF-kB transcription factors, thereby resulting in inhibition of protein expression which works a significant part in cell proliferation. Therefore, the BATU compound has the potential to be developed as a complementary drug in breast cancer therapy with HER-2 positive.

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