Identification of selective bioactive compounds from Fenugreek seed extracts by GC-MS analysis and their anti-tumoral potential via modulation of Parkin in oral cancer.

Abstract

Oral cancer (OC) is a serious health concern globally. Various pieces of evidence have observed that the primary aetiology of OC in an individual is molecular-level dysregulation via several processes in multiple tumour suppressor genes (TSGs), including p53, PTEN, FOXO, and Parkin, leading to variations in their expression levels. Parkin, an E3 ubiquitin ligase, was primarily recognized as a gene implicated in autosomal recessive juvenile Parkinsonism; nonetheless, several studies show that Parkin is a TSG, involved in several malignancies. In the present study, we have first explored the role of Parkin against oral cancer. Current conventional anti-cancer therapies cause several harmful side effects, are costly in nature and also time-consuming. Therefore, it is crucial to explore alternative natural therapeutic approaches which can impede or slow the progression of OC by regulating TSG expression. In recent times, plant-derived bioactive compounds might be used as natural therapeutic approaches to curb OC by regulating TSGs. Using medicinal plants and their parts can be a reliable and efficient option with no or minimal side effects. Fenugreek is one of the nature-gifted plants that exhibits several health-beneficial properties, including anti-cancer. The current investigation primarily addressed the anti-cancer properties of bioactive compounds derived from Fenugreek seeds and their interaction with Parkin to combat OC, which remains unexplored. The current study employs various methods to examine the anti-tumor effects of ten bioactive compounds out of 75 constituents, including Gas Chromatography-Mass Spectrometry, in vitro studies, MTT assay, DNA fragmentation, and ELISA, while in-silico studies, ADME/T, molecular docking and dynamic simulation. The results show that Diosgenin exhibited drug-like attributes, which inhibited human KB cell proliferation (273.47 µg/mL) in 24 h and contained high binding affinity and a more stable complex with Parkin protein - 8.9kcal/molthanstandarddrug,Doxorubicin -8.0 kcal/mol inspected bydockingand H-bonds, RMSD, RMSF, RG, and SASA by simulation studies. These findings have revealed that OC treatment with Diosgenin may be a promising potent anti-cancer drug. Hence, current studies can be useful in the development of safe and non-toxic therapeutic regimen to prevent OC.