c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy.

BACKGROUND: c-MET is a receptor tyrosine kinase which is classically activated by HGF to activate its downstream signaling cascades such as MAPK, PI3K/Akt/mTOR, and STAT3. The c-MET modulates cell proliferation, epithelial-mesenchymal transition (EMT), immune response, morphogenesis, apoptosis, and angiogenesis. The c-MET has been shown to serve a prominent role in embryogenesis and early development. The c-MET pathway is deregulated in a broad range of malignancies, due to overexpression of ligands or receptors, genomic amplification, and MET mutations. The link between the deregulation of c-MET signaling and tumor progression has been well-documented. Overexpression or overactivation of c-MET is associated with dismal clinical outcomes and acquired resistance to targeted therapies. Since c-MET activation results in the triggering of oncogenic pathways, abrogating the c-MET pathway is considered to be a pivotal strategy in cancer therapeutics. Herein, an analysis of role of the c-MET pathway in human cancers and its relevance in bone metastasis and therapeutic resistance has been undertaken. Also, an attempt has been made to summarize the inhibitory activity of selected natural compounds towards c-MET signaling in cancers. METHODS: The publications related to c-MET pathway in malignancies and its natural compound modulators were obtained from databases such as PubMed, Scopus, and Google Scholar and summarized based on PRISMA guidelines. Some of the keywords used for extracting relevant literature are c-MET, natural compound inhibitors of c-MET, c-MET in liver cancer, c-MET in breast cancer, c-MET in lung cancer, c-MET in pancreatic cancer, c-MET in head and neck cancer, c-MET in bone metastasis, c-MET in therapeutic resistance, and combination of c-MET inhibitors and chemotherapeutic agents. The chemical structure of natural compounds was verified in PubChem database. RESULTS: The search yielded 3935 publications, of which 195 reference publications were used for our analysis. Clinical trials were referenced using ClinicalTrials.gov identifier. The c-MET pathway has been recognized as a prominent target to combat the growth, metastasis, and chemotherapeutic resistance in cancers. The key role of the c-MET in bone metastasis as well as therapeutic resistance has been elaborated. Also, suppressive effect of selected natural compounds on the c-MET pathway in clinical/preclinical studies has been discussed.

Green technology approach for heavy metal adsorption by agricultural and food industry solid wastes as bio-adsorbents: a review.

Heavy metal discharge from various metallurgical industries has been of particular concern in India over the last few decades. Similarly, management and disposal of wastes that are generated out of agricultural commodities processing is a huge task for processors. The researchers have been focusing on a new process for remediation of heavy metals, among which biosorption is an emerging technology. Adsorption using agricultural and food industry wastes (AFW) has shown a greater absorption rate than the conventional system due to the presence of the functional groups. In addition, these reported AFW exhibited better adsorption efficiency when modified with acid, alkaline, and other chemical solvents. In this context, utilization of agricultural and food waste as bio-sorbent could simultaneously benefit both water treatment and waste management. This review seeking to address the possibilities of using biosorption as green technological approach for removal of heavy metals and also focuses on various parameters that are required to use AFW as an efficient system for biosorption. However, commercialization and implementation of this process in industrial scale is necessary for successfully utilizing AFW as low-cost adsorbents. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05486-1.