Dose-dependent inhibition of tumor spheroid growth by sodium bicarbonate

The altered metabolism of malignant cells compared to normal cells leads to acidification of the tumor microenvironment in solid tumors, creating conditions that promote their accelerated growth and aggressiveness. Strategies to neutralize or alkalize the tumor microenvironment using buffering agents such as sodium bicarbonate represent a promising approach in cancer metabolic therapy. However, in vitro data on such effects are limited and have mainly been conducted on cell monolayers. Tumor spheroids are three-dimensional cellular models that more accurately recapitulate the properties of solid tumors in experimental settings. In the present study, we examined the effects of various sodium bicarbonate concentrations on the growth, viability, and metabolic activity of spheroids formed from mouse CT26 colon adenocarcinoma cells, mouse 4T1 breast carcinoma cells, and human melanoma cells. Increasing sodium bicarbonate concentration in the culture medium induced a dose-dependent suppression of spheroid growth across all tumor types. Simultaneously, glucose consumption and lactic acid (lactate) production increased, indicating the onset of uncompensated metabolic stress. The universality of this observed effect across spheroids derived from three distinct tumor cell lines underscores the potential of alkalization therapy for cancer treatment.