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.
Highlights
Breast cancer is the most common type of cancer in women and is the leading cause of cancer death in females worldwide [1,2]
We investigated the effect of exogenous pH on the growth, death, intracellular reactive oxygen species (ROS) levels and cell cycle of MDA-MB-231 cells, a triple-negative breast cancer cell line characterized by high aggressiveness and invasiveness
In order to understand the effect of the different pHe on breast cancer cells, we incubated triple-negative breast cancer cells (MDA-MB-231) in various pH media, and we monitored their growth profile, death, intracellular ROS levels, cell cycle and extracellular pH changes
Summary
Breast cancer is the most common type of cancer in women and is the leading cause of cancer death in females worldwide [1,2]. Not all breast cancer cells are the same. 70–80 percent of breast cancers are hormone receptor positive and express ER or PR [5]. Hormone-receptorpositive breast cancers can be treated with hormone therapy drugs. Breast cancer cells that do not express any of these three receptors are called triple negative and are usually highly aggressive. They cannot be treated with hormone therapy drugs [6]
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