Small Molecular Leads Differentially Active Against HER2 Positive and Triple Negative Breast Cancer Cell Lines

Author(s): Adnan Badran*, Atia-tul-Wahab*, Sharmeen Fayyaz, Elias Baydoun, Muhammad Iqbal Choudhary*

Journal Name: Medicinal Chemistry

Volume 15 , Issue 7 , 2019

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Graphical Abstract:


Background: Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.

Methods: The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.

Results: Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.

Conclusion: These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.

Keywords: Anti-cancer, breast cancer, Human Epidermal Growth Factor Receptor-2 (HER2), estrogen receptors, heterocyclic compounds, convallatoxin.

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Article Details

Year: 2019
Published on: 06 November, 2018
Page: [738 - 742]
Pages: 5
DOI: 10.2174/1573406414666181106143912
Price: $65

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