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2nd Edition of International Precision Medicine Conference

April 21-23, 2022

April 21 -23, 2022 | Las Vegas, Nevada, United States
2021 Speakers

Calcium-sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer Cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin ?1 and Induces Caspase 3/7 Activation

Mohammad A Y Alqudah, Speaker at
Jordan University of Science and Technology, Jordan
Title : Calcium-sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer Cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin ?1 and Induces Caspase 3/7 Activation

Abstract:

Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the bone. Targeting chemoattractant factors, such as calcium, that are released in response to bone resorption could prevent metastasis and induce apoptosis of cancer cells. In the present study, we investigated the potential caspase 3/7 activation following treatment with a CaSR antagonist, NPS-2143, in breast cancer cells. In addition, the effects of NPS-2143 on breast cancer cell proliferation, migration and invasion were assessed.

Methods: Colorimetric MTT assay was used to evaluate cell viability. Apo-one homogeneous caspase-3/7 assay was used to measure caspase 3/7 activities in breast cancer cells. Cell migration and invasion were assessed using scratch wound assay and matrigel invasion chambers, respectively. The protein expressions of p-ERK1/2, integrin β1 and Bcl-2 were evaluated using western blotting.

Results: Our study revealed that NPS-2143 significantly reduced cell proliferation with half maximal (50%) inhibitory concentration (IC50) values of 4.08 and 5.71 µM in MDA-MB-231 and MCF-7 cells, respectively. NPS-2143 induced caspase 3/7 activation in MDA-MB-231 breast cancer cells which was accompanied with a remarkable reduction in the expression of Bcl-2 antiapoptotic protein. NPS-2143 suppressed migratory and invasive abilities of MDA-MB-231 cells with a significant reduction in the expression of p-ERK1/2 and integrin β1 proteins.

Conclusion: Our study confirms the ability NPS-2143 to suppress proliferative, migratory and invasive effects of breast cancer cells which was accompanied by caspase 3/7 activation and suggests the potential of NPS-2143 as a promising anti-cancer molecule in breast cancer.

Biography:

Dr. Mohammad A Y Alqudah is an Associate Professor in the college of pharmacy at Jordan University of Science and Technology (JUST) where he has been a faculty member since 2013. In addition, he is a chairman of clinical pharmacy department at King Abdullah University Hospital.

Dr. Alqudah completed his PhD at the University of Iowa and his PharmD at JUST. His research interests lie in cancer therapeutics ranging from basic science to pharmacogenomics. He has published more than 20 research articles in SCI(E) and Scopus journals.

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