Current Perspectives of Matrix Metalloproteinase 11 (MMP11) as a Diagnostic and Therapeutic Target for Cancer Asokan Shobana, Remella Venkata Deeksha, Syed Ali Abdul Rahman, Tiviya Thangaswamy, Revathi Paramasivam Oviya, Gopal Gopisetty Current Cancer Therapy Reviews, 2024 Matrix metalloproteinase 11 (MMP11), also known as stromelysin-3, is a member of the matrix metalloproteinases family of proteins that are involved in physiological and pathological extracellular matrix remodelling. MMP11 does not hydrolyse classical MMP substrates, such as laminin and fibronectin, and many of its substrates remain unknown, piquing the interest of researchers. Several studies have reported the role of MMP11 in inducing tumour growth by inhibiting apoptosis and promoting cancer cell migration and invasion. Various reports have shown its potential as a diagnostic and prognostic marker in a majority of cancers. MMP11 also induces an immune response as a tumour-associated antigen, and recent evidence shows the involvement of many microRNAs in targeting MMP11 in cancer, with prospective future applications in cancer immunotherapy and gene silencing. Owing to the importance of MMP11 in both cancer diagnosis and therapy, there is a need for deeper understanding of its mechanism and role in tumour progression. The current review focuses on the role of MMP11 in cell signalling pathways, its expression status in various cancers, and its potential in cancer treatment.
Analysis of bioactive compounds from Gracilaria foliifera based on lunar phases P. Prakash, S. Krishna, S. Sunkar, O. R. Paramasivam, K. Rajakumari Indian Journal of Geo Marine Sciences, 2022 Gracilaria foliifera, sustainable renewable resources in the marine environment. Gracilaria , a genus of red algae, notable for its economic importance as an agarophyte. In the present study, experiments were performed to investigate the phytochemical constituents of Gracilaria foliifera . Samples were collected during three different lunar phases namely new moon, full moon and between days. The collected seaweeds were shade dried and extracted by ethyl acetate. The crude metabolites are subjected to phytochemical analysis, antioxidant activity, and qualitative analysis of the compounds by TLC. Further the crude extract was evaluated by GCMS. Among the different lunar phases, the presence of phytochemical compounds, antioxidants activity, is maximum during the full moon days which also showed appreciable amount than the samples collected during new moon phase and transition phase.
Expression and affinity purification of recombinant mammalian mitochondrial ribosomal small subunit (MRPS) proteins and protein-protein interaction analysis indicate putative role in tumourigenic cellular processes Oviya Revathi Paramasivam, Gopal Gopisetty, Jayavelu Subramani, Rajkumar Thangarajan Journal of Biochemistry, 2021 Mitochondrial ribosomal small subunit (MRPS) group of proteins is structural constituents of the small subunit of mitoribosomes involved in translation. Recent studies indicate role in tumourigenic process, however, unlike cytosolic ribosomal proteins, knowledge on the role of MRPS proteins in alternate cellular processes is very limited. Mapping protein–protein interactions (PPIs) onto known cellular processes can be a valuable tool to identify novel protein functions. In this study, to identify PPIs of MRPS proteins, we have constructed 31 glutathione-S-transferase (GST)/MRPS fusion clones. GST/MRPS fusion proteins were confirmed by MALDI-TOF analysis. GST pull-downs were performed using eight GST/MRPS proteins (MRPS9, MRPS10, MRPS11, MRPS18B, MRPS31, MRPS33, MRPS38 and MRPS39), GST alone as pull-down control and HEK293 cell lysate as the source for anchor proteins followed by nLC/MS/MS analysis and probable PPIs of eight MRPS proteins were identified. Three PPIs from GST pull-downs and interaction between six MRPS proteins and p53 previously reported in PPI database were validated. The PPI network analysis revealed putative role in cellular processes with implications for tumourigenesis. Gene expression screening of a cancer cell line panel indicated overexpression of MRPS10 and MRPS31 in breast cancer. Co-expression module identification tool analysis of breast cancer gene expression and MRPS10 and MRPS31 PPIs revealed putative role for PPI with acyl-CoA dehydrogenase in fatty acid oxidation process regulated by brain-derived neurotrophic factor signalling pathway.
Subcellular organelle targeting of mitochondria using nanomed-icines: Cancer therapeutics and theranostics potential R. Oviya, G. Gopal Current Nanomedicine, 2020 Nanomedicines are rapidly evolving in chemotherapy and image-guided theranostics for specific and controlled delivery of the target therapeutic molecule. Targeting the subcellular organelles of cancer cells has gained focus in the recent decade for precise targeting of cancer cells and the activation of specific cancer death pathways. This strategy also overcomes the limitations of conventional chemo and radiation therapies, such as non-specificity and toxicity to the surrounding healthy tissue. Diverse roles of mitochondria in cancer, including oxidative stress signaling, metabolic reprogramming, cell death evasion, and cell survival mechanism, make it a promising target for cancer therapy. However, targeting mitochondria is tedious due to its complex structure and strong negative membrane potential. Various studies have designed mitochondria specific inorganic-, polymer-, dendrimer-, peptide- and protein-based nanoformulations to overcome barriers in targeting mitochondria of cancer cells. In this review, we have summarized the recently developed mitochondria-targeted nanoformulations in the field of chemotherapy, imageguided phototherapy, and combinatorial therapies. These nanoformulations showed enhanced cell penetration and mitochondrial accumulation of the drug molecules. In vitro and in vivo studies have shown promising results and further pre-clinical and clinical studies are required to develop these nanoformulations as effective cancer therapy.
Production and characterization of monoclonal antibodies against recombinant extracellular domain of CD99 Krishna Priya Thangaretnam, Oviya Revathi Paramasivam, Priya Ramanathan, Gopal Gopisetty, Thangarajan Rajkumar Human Antibodies, 2018 BACKGROUND AND OBJECTIVE CD99/MIC2 gene product is a heavily glycosylated transmembrane protein which plays a major role in homotypic cell adhesion, apoptosis of double positive T cells and vesicular protein trafficking. It is over expressed in various cancers and has been considered as an ideal therapeutic target. The present study focused at developing monoclonal antibodies against the extracellular domain (ECD) of CD99 using hybridoma technology. MATERIALS AND METHODS In order to generate monoclonal antibodies, the recombinant ECD of CD99 was used for immunizing the mice. Resulting hybridomas were screened through indirect ELISA. Clones which gave high absorbance values were sub cloned by limiting dilution followed by isotype determination, IP, WB and FACS. The monoclonal antibody 547F2 4F12 was purified from culture supernatant using FPLC and further screened using IF. Finally, the antibodies were validated for specificity using siRNA knock-down. RESULTS We were able to establish stable hybridoma clones secreting CD99 antibodies. The antibodies reacted with both the recombinant ECD as well as the wild type CD99 and their isotype's were determined as IgM. CONCLUSION Based on these results, we propose that the purified monoclonal antibody 547F2 4F12 could be possibly used for targeting tumors which over express CD99.
