Hydrogen phosphate selectively induces MDA MB 231 triple negative breast cancer cell death in vitro
Aya Shanti1, Kenana Al Adem1, Cesare Stefanini1
1Department of Biomedical Engineering, Healthcare Engineering Innovation Center, Khalifa University of Science and Technology, 127788, Abu Dhabi, United Arab Emirates.
Abstract:
Phosphate ions are the most abundant anions inside the cells, and they are increasingly gaining attention as key modulators of cellular function and gene expression. However, little is known about the effect of inorganic phosphate ions on cancer cells, particularly breast cancer cells. Here, we investigated the toxicity of different phosphate compounds to triple-negative human breast cancer cells, particularly, MDA-MB-231, and compared it to that of human monocytes, THP-1. We found that, unlike dihydrogen phosphate (H2PO4-), hydrogen phosphate (HPO42-) at 20 mM or lower concentrations induced breast cancer cell death more than immune cell death, mainly via apoptosis. We correlate this effect to the fact that phosphate in the form of HPO42- raises pH levels to alkaline levels which are not optimum for transport of phosphate into cancer cells. The results in this study highlight the importance of further exploring hydrogen phosphate (HPO42-) as a potential therapeutic for the treatment of breast cancer.
Insights
Hydrogen phosphate (HPO4^2-) selectively induces apoptosis in triple-negative breast cancer cells (MDA-MB-231) at lower concentrations than dihydrogen phosphate (H2PO4^-). This finding suggests HPO4^2- as a potential therapeutic for breast cancer.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Phosphate ions are crucial intracellular anions regulating cellular functions and gene expression.
- The specific effects of inorganic phosphate on cancer cells, especially breast cancer, remain largely uncharacterized.
Purpose of the Study:
- To investigate the differential toxicity of various phosphate compounds on triple-negative human breast cancer cells (MDA-MB-231) compared to human monocytes (THP-1).
- To explore the potential of hydrogen phosphate (HPO4^2-) as a therapeutic agent for breast cancer treatment.
Main Methods:
- Differential toxicity assays were performed using MDA-MB-231 and THP-1 cell lines.
- Exposure to varying concentrations of dihydrogen phosphate (H2PO4^-) and hydrogen phosphate (HPO4^2-).
- Apoptosis induction was assessed as a primary mechanism of cell death.
Main Results:
- Hydrogen phosphate (HPO4^2-), but not dihydrogen phosphate (H2PO4^-), induced significant cancer cell death at concentrations of 20 mM or lower.
- Cancer cell death induced by HPO4^2- was notably higher than immune cell death.
- The mechanism of cancer cell death was primarily attributed to apoptosis, potentially linked to intracellular pH alterations.
Conclusions:
- Hydrogen phosphate (HPO4^2-) exhibits selective toxicity towards triple-negative breast cancer cells.
- The observed alkaline shift in pH due to HPO4^2- may impede its transport into cancer cells, contributing to selective toxicity.
- HPO4^2- warrants further investigation as a promising therapeutic strategy for breast cancer.
