In vitro quantification: Long-term effect of glucose deprivation on various cancer cell lines.

Objective: Although metabolic treatment of highly glycolytic cancers and metastases is becoming an important research field, the effects of such treatments are not fully quantified yet. In this article we attempt to quantify the effect of long-term glucose deprivation (similar to ketogenic diets) on cancer cells using in vitro tests.

Methods: Two tumorigenic cell lines were used, namely a metastatic breast and a cervical cancer cell line. The non-tumorigenic control cell line was an immortalized breast cell line. All the cell lines were stabilized at a typical average human blood glucose level of 6 mmol/L. The cell lines were then exposed to the therapeutic blood glucose level of 3 mmol/L for 90 d.

Results: The tests indicated that glucose deprivation restricted the different cancer cell lines' growth more than that of non-tumorigenic cells. The different cell lines were also differentially affected, which suggests that long-term glucose deprivation will not be equally effective for different types of cancer. The highly glycolytic breast cancer cell line was most adversely affected, with cell growth decreasing to 30% after 26 d. Cell growth was stable at this level for up to 22 d. Furthermore, all of the other cancer cell lines were similarly affected.

Conclusions: This in vitro data could help to direct future human in vivo tests to find the most therapeutic time (cancer cells at their most vulnerable) for additional short-term adjuvant therapies. Partial recovery of proliferation occurred after 90 d. Therefore, as expected, the results also indicated that without an adjuvant treatment, full extinction cannot be reached with the proposed long-term metabolic treatment. The need for more clinical data on long-term glucose deprivation treatments for cancer is well described in the literature. This paper attempts to add to the available pool of knowledge.