lactate dehydrogenase A inhibition via peptides to regulate the Warburg effect: cell signaling analysis

Lactate dehydrogenase A (LDHA) plays a critical role in the Warburg effect that is detectedin numerous types of solid tumors. Hence, LDHA has been proposed as a potential target for suppressionin the field of cancer treatments. Here, we used in-silico study to design inhibitory peptide for LDHA.After that, we checked the effect of peptide on cell signaling in Balb/c mice. The expression levels ofthree proteins, namely cdc۲۰, cdk۲, and Rb۱, were analyzed in tumor tissue samples obtained from boththe control and treatment groups. The findings indicate a decrease in the expression levels of cdc۲۰ andcdk۲ in the treatment groups. However, the expression of Rb۱ was shown to be significantly higher inthe treatment groups when compared to both the control and sham groups. The inactivation of the RB۱is a common occurrence in cancer, either through direct mutations or indirectly through thedysregulation of RB۱ regulators [۱]. On the other hand, activation of CDK۲ is associated with theprogression of malignancy and the invasive behavior of cancer cells [۲]. Other study was shown thatinhibiting mitotic exit by the downregulation of CDC۲۰ proved to be a more effective approach ineliminating cancer cells [۳]. Therefore, increases of Rb۱ and decreases of cdc۲۰ and cdk۲ expressionindicated the effect of peptide in cancer treatment. Finally, discovering of these peptides may be a newway for dealing with cancer, and we will decide to optimize these peptides in future work.

کلیدواژه ها:

Lactate dehydrogenase A ، Warburg effect ، peptide inhibitors ، therapeutic targets ، cancer