Cancer cells have a high ROS content that causes glycolysis (W Warburg} effect. CSCs, (cancer cells) {Cancer Stem Cells} that are induced in response to oxidative stress, have enhanced metabolism of PPP {Pentose Phosphate Pathway}. Thus the cancer cells, after increasing the ROS level, deviate from the glycolysis to the PPP pathway and this metabolic deviation (after persistent oxidative stress translates as a step of the cancer cells turning into CSCs).
Cancer cells can adapt to low energy sources in view of ATP depletion, as well as high ROS levels, altering the metabolic and energy production networks that can determine cell fate and the development of drug resistance. Cancer cells are generally characterized by increased glycolysis, while CSCs show increased PPP pathway metabolism. In summary, cancer cells when exposed to ROS, first increase the rate of glycolysis and then, with continuing oxidative stress, the metabolic balance is converted from glycolysis to PPP. So this metabolic deviation during persistent oxidative stress is a sign of cancer cell shifting to CSCs.
The pentose phosphate pathway is a metabolic pathway parallel to glycolysis, producing NADPH {oxidative phase} and non-oxidative for the synthesis of 5-carbon sugars, {pentoses} for nucleotide synthesis. The pentose phosphate (PPP) pathway plays a key role in maintaining high cell proliferation and represents an advantage for cancer cells. PKM2 expression has been used as a tumor marker, which it is associated with tumor metabolism and tumor growth. PKM2 is proposed as a therapeutic target for cancer treatment and drugs that suppress it also inhibit cancer metabolism.
NOTE: Resveratrol, curcumin, and epigallocatechin (EGCG) suppress PKM2 (determined by ELISA and flow cytometry).
SOURCE: Biomedicine & Pharmacotherapy {April 2019}
