Natural antioxidants as inhibitors of pyruvate kinase M2 in Warburg phenotypes

Introduction: Cancer is still the foremost cause of death, impacting globally. Novel chemotherapeutic drugs with higher efficiency are needed to supplement current treatment modalities for improving cancer survival rates, especially in metastasised cancer. Phytochemicals, naturally occurring plant compounds, are promising agents with a significant antitumor activity that can avert, inhibit, delay, or cure cancer. In the metabolism of cancer, the key glycolytic enzyme Pyruvate kinase M2 (PKM2) is known to predominate and play a vital role. The current review aimed to compile data from various databases to understand the Warburg effect and its key glycolytic enzyme controlling cancer energy metabolism and how different plant molecules inhibit the enzyme activity of PKM2. Methodology: To support these findings, several researchers used in-vitro and in-silico models. A literature review on metabolism of cancer, PKM2 and various phytochemical constituents inhibiting PKM2 was conducted utilising online databases between 1922 and 2021.Results: Sixteen plant based inhibitors of PKM2 were identified, targeting metabolic and oncogenic pathways. Discussion: There is a lot of potential for using polyphenolic compounds to develop goods that mitigate the effects of oxidative stress and provide significant health advantages. Since Pyruvate kinase M2 interacts with cancer metabolism and offers a potential therapeutic approach in the field of oncology, this narrative review highlights many phytochemicals that target it in diverse malignancies.Conclusions: Few phytochemicals have been proven to interfere with cancer metabolism. More natural compounds need to be screened for their detrimental effects on critical regulators of cancer metabolism.

Automated summary

This article summarizes the research progress in using phytochemicals to inhibit the key glycolytic enzyme PKM2 in cancer treatment. By analyzing data from multiple databases, 16 plant-based inhibitors were identified, which can target metabolic and oncogenic pathways and have potential therapeutic effects on various malignancies. However, further screening of more natural compounds is needed to study their effects on cancer metabolism.