Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme

Rushikesh Patel, Ajay Kumar Raj, Kiran Bharat Lokhande, Mazen A. Almasri, Khalid J. Alzahrani, Asma Saleh Almeslet, K. Venkateswara Swamy, Gargi S. Sarode, Sachin C. Sarode, Shankargouda Patil and Nilesh Kumar Sharma
Additional contact information
Rushikesh Patel: Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India
Ajay Kumar Raj: Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India
Kiran Bharat Lokhande: Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India
Mazen A. Almasri: Oral and Maxillofacial Surgery Department, King Abdulaziz University, Jeddah City 21589, Saudi Arabia
Khalid J. Alzahrani: Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Asma Saleh Almeslet: Oral and Maxillofacial Surgery and Diagnostic Sciences Department, Riyadh Elm University, Riyadh 12611, Saudi Arabia
K. Venkateswara Swamy: MIT-School of Bioengineering Sciences & Research, MIT-Art, Design and Technology University, Pune 412201, Maharashtra, India
Gargi S. Sarode: Department of Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, India
Sachin C. Sarode: Department of Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, India
Shankargouda Patil: Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia
Nilesh Kumar Sharma: Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India

IJERPH, 2021, vol. 18, issue 21, 1-11

Abstract: Oncometabolites are known to drive metabolic adaptations in oral cancer. Several oncometabolites are known to be shared between cancer cells and non-cancer cells including microbiotas to modulate the tumor microenvironment. Among potential oncometabolites, succinylaminoimidazolecarboxamide ribose5?-phosphate (SAICAR) supports the growth and invasiveness of cancer cells by pyruvate kinase M2 (PKM2) enzyme in a glucose starved tumor microenvironment. There is a significant gap that shows the detection of SAICAR in biological samples including nails of oral cancer patients. Metabolite identification of SAICAR was investigated in the nails of oral cancer patients using novel vertical tube gel electrophoresis (VTGE) and LC-HRMS. Further molecular docking and molecular dynamics simulations (MDS) were employed to determine the nature of molecular interactions of SAICAR (CHEBI ID:18319) with PKM2 (PDB ID: 4G1N). Molecular docking of SAICAR (CHEBI ID:18319) was performed against pyruvate kinase M2 (PDB ID: 4G1N). Data suggest the presence of oncometabolite SAICAR in nails of oral cancer. Molecular docking of SAICAR with PKM2 showed appreciable binding affinity (?8.0 kcal/mol) with residues including ASP407, THR405, GLU410, ARG443, GLY321, ARG436, HIS439, LYS266, and TYR466. Furthermore, MDS confirmed the specific binding of SAICAR within the activator site of PKM2 and the stability of SAICAR and PKM2 molecular interactions. In conclusion, SAICAR is a promising oncometabolite biomarker present in the nails of oral cancer patients. A significant activation potential of SAICAR exists with the PKM2 enzyme.

Keywords: oral cancer; metabolite biomarkers; SAICAR; pyruvate kinase M2; in silico studies (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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