National Brain Research Centre

Dr. Ellora Sen and her team at NBRC

A new body clock-based approach likely for cancer treatment

New Delhi, July 12:  A study by a team of researchers at the Government of India’s Department of Biotechnology’s Manesar-based National Brain Research Centre (NBRC) has helped gain new insights into molecular mechanisms involved in the proliferation of cancer cells, which may aid in the treatment of cancers based on the body clock. The human biological clock is composed of several molecular mechanisms which are synchronous with the day-night cycle or circadian rhythm. Disruption in the cycle can lead to chronic metabolic disorders. Among other things, the circadian rhythm keeps a check on the proliferation of cells in the body. However, when cells become cancerous, they break away from the circadian rhythm and escape from the circadian control system to undergo uncontrolled proliferation. The processes that promote cancerous growth can hijack the metabolic balance to fuel the rapidly proliferating cancer cells. The dysregulated metabolic balance in cancer cells results in the increased generation of a substance called lactate.  Further, cancer cells produce large quantities of a protein called IL-1β that promotes the growth of tumours. Till now, it was not clear how cancer cells sustain the high rate of production of lactate and IL-1β in conjunction with the cellular circadian rhythm. The researchers at NBRC have now unravelled the mystery. They have found that cancer cells modify the molecular components of cellular circadian rhythm to create a new regulatory network that produces more lactate and IL-1β. The network has been named as Lactate-Inflammation-Clock (LIC).   In their first set of experiments, the research team used chemicals to activate/inhibit lactate and IL-1β in glioma cells, a type of tumour that occurs in the brain and spinal cord. They found that, when activated, lactate and IL-1β induce the expression of important circadian proteins called Clock and Bmal1. Further molecular experiments revealed that Clock/Bmal1 transcriptionally activates the expression of LDH-A (Lactate producing enzyme) and IL-1β thus confirming the existence of the LIC regulatory network. The team found that LIC controls the key pathways of glioma progression such as cell cycle, DNA damage and repair of cytoskeletal architecture and modification of chromatin, which is…