Conference Proceeding

Methylglyoxal: a unique molecule for cancer therapy

Dr. Manju Ray,
Bose Institute, India

Manju Ray carried out her Post - doctoral research in University of Calcutta, India. Later she started working as a Honorary Visiting Professor in Bose institute kolkata, India. She has many honors and awards. Presently she is working as Emeritus Scientist in Bose Institute, kolkata, India.

Methylglyoxal (MG), a ketoaldehyde, has been known for anti-cancer and growth regulatory properties exclusively in malignant cells without affecting normal cells. Its tumoricidal activity is due to its efficiency in depleting the cellular ATP pool by inhibition of ATP generating enzymes, especially of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and mitochondrial complex I. The selective inhibitory effects of MG are due to specific structural differences in mitochondrial complex I and GAPDH between normal and malignant cells. The convincing demonstrations of difference between normal and malignant cells have led to significant development of an effective non-toxic anticancer formulation based on methylglyoxal. The toxicity was assessed by administering MG to different species of animals. Methylglyoxal enhances the non-specific immunity of the host against tumor cells. MG increases the number of peritoneal macrophages and also elevates the phagocytic capacity of macrophages in both normal and tumor-bearing mice. This activation is due to increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs) which can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. Different cytokines such as IFN-γ, TNF-α, IL-6 etc were found to be elevated by methylglyoxal. Methylglyoxal also plays an important role in the proliferation and cytotoxicity of splenic lymphocytes. Surface markers such as CD4 and CD8 also showed increased expression by MG treatment. MG-based anticancer formulation was administered orally to diverse groups of cancer patients with the due permission from regulatory authorities. Highly encouraging and promising results had been published. Phase II/III clinical trial of the formulation on cancer patients are on the way to completion.

Published: 11 May 2017