Effect of Exogenous pH on Cell Growth of Breast Cancer Cells

Abstract

Breast cancer is the most common type of cancer in women and the most life-threatening cancer in females worldwide. One key feature of cancer cells, including breast cancer cells, is a reversed pH gradient which causes the extracellular pH of cancer cells to be more acidic than that of normal cells. Growing literature suggests that alkaline therapy could reverse the pH gradient back to normal and treat the cancer; however, evidence remains inconclusive. In this study, we investigated how different exogenous pH levels affected the growth, survival, intracellular reactive oxygen species (ROS) levels and cell cycle of triple-negative breast cancer cells from MDA-MB-231 cancer cell lines. Our results demonstrated that extreme acidic conditions (pH 6.0) and moderate to extreme basic conditions (pH 8.4 and pH 9.2) retarded cellular growth, induced cell death via necrosis and apoptosis, increased ROS levels, and shifted the cell cycle away from the G0/G1 phase. However, slightly acidic conditions (pH 6.7) increased cellular growth, decreased ROS levels, did not cause significant cell death and shifted the cell cycle from the G0/G1 phase to the G2/M phase, thereby explaining why cancer cells favored acidic conditions over neutral ones. Interestingly, our results also showed that cellular pH history did not significantly affect the subsequent growth of cells when the pH of the medium was changed. Based on these results, we suggest that controlling or maintaining an unfavorable pH (such as a slightly alkaline pH) for cancer cells in vivo could retard the growth of cancer cells or potentially treat the cancer.

Effects of Lactobacillus acidophilus KLDS1.0901 on Proliferation and Apoptosis of Colon Cancer Cells

“…It shows that the extracts of strains LB3 and LB5 have high cytotoxicity on Caco-2 cells with IC50 40.8 and 51 µg/mL, respectively. Cancer cells have a lower extracellular pH of 6.7-7.1 and a higher intracellular pH of 7.4, whereas normal cells have a higher extracellular pH of 7.4 and a lower intracellular pH of 7.2(Lee and Shanti, 2021).Li et al…”

Different Serum, Different Protein Corona! The Impact of the Serum Source on Cellular Targeting of Folic Acid-Modified Chitosan-Based Nanoparticles

“…Lee et al demonstrated that medium alkalinity resulted in a combination of effects in MDA-MB231 cells, retardation of cellular growth, induction of cell death via necrosis and apoptosis, and a shift in the cell cycle away from the G0/G1 phase. On the other hand, slightly acidic conditions increased cellular growth and did not cause significant cell death . Within the same context, after 48 h culture of human CD24-/CD44+ breast cancer stem cells, the growth rate was slower (13.3 × 10 5 viable cells) when compared to the nonalkalinized culture (25.2 × 10 5 viable cells) …”

“…On the other hand, slightly acidic conditions increased cellular growth and did not cause significant cell death. 48 Within the same context, after 48 h culture of human CD24-/CD44+ breast cancer stem cells, the growth rate was slower (13.3 × 10 5 viable cells) when compared to the nonalkalinized culture (25.2 × 10 5 viable cells). 49 Additionally, FACS analysis also revealed that that when cultured in the presence of BrCr Pt serum, MCF-7 cell apoptosis is diminished relative to FBS and serum from HV (Figure 2B,C).…”

Nanoaggregates of Biphilic Carboxyl-Containing Copolymers as Carriers for Ionically Bound Doxorubicin

“…Thus, the pH effect on the drug release rate is associated with an increase in the proportion of non-immobilized doxorubicin in the salt (in an acidic medium) or basic form (in an alkaline medium). On the other hand, it is known that cancer cells are often characterized by a lower pH value compared to normal cells [ 58 , 59 ]. However, the main difference between cancer cells and normal cells is the high intensity of metabolic processes and an increased rate of endocytosis, which is realized through specific mechanisms such as macro-pinocytosis [ 60 ].…”