Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics.
Dwaipayan BhattacharyaMadhu Rani BharatiKalyani SakharePiyush KhandeliaRajkumar BanerjeeKumar Pranav NarayanPublished in: Biomedical materials (Bristol, England) (2024)
Glucocorticoid and Mineralocorticoid receptors are principally ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. Our study investigates the potential of these receptors to act as a target for oral cancer treatment since findings in this regard are sparse till date. Leveraging the aberrant behaviour of SHRs (Steroid Hormone Receptors) in cancer, we have targeted oral cancer cells in 2D-culture using liposomes containing both synthetic as well as crude, natural SHR ligands isolated from an aqueous Indian medicinal plant. Lipoplexes thus formulated demonstrated targeted transfectability as indicated by expression of GFP (Green Fluorescent Protein). Transfection of OSCC cells with exogenous, anticancer gene p53 lipoplexed with crude saponin-based liposome induced apoptosis of cancer cells via regulation of BAX and BCL2 protein levels at levels comparable with pre-established delivery systems based on synthetic SHR ligands. Our findings strongly indicate a possibility of developing plant saponin-based inexpensive delivery systems which would target cancer cells selectively with reduced risks of off target delivery and its side effects.
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Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- human health
- transcription factor
- genome wide identification
- binding protein
- poor prognosis
- copy number
- endothelial cells
- genome wide
- cancer therapy
- drug delivery
- protein protein
- amino acid
- quantum dots
- reactive oxygen species
- squamous cell
- squamous cell carcinoma
- gene expression
- lymph node metastasis
- cell wall
- neural network
- single molecule