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DNA Vector-based RNA Interference to Study Gene Function in Cancer
Published on: June 4, 2012
Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics
Dwaipayan Bhattacharya1, Madhu Rani Bharati1, Kalyani Sakhare1
1Department of Biological Science, Birla Institute of Technology & Science Pilani, Hyderabad Campus, Jawaharnagar, Kapra Mandal, Hyderabad, Telangana 500078, India.
Abstract:
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 behavior of steroid hormone receptors (SHRs) 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 green fluorescent protein. Transfection of oral squamous cell carcinoma cells with exogenous, anticancer gene p53 lipoplexed with crude saponin-based liposome induced apoptosis of cancer cells via regulation of BAX and B-cell leukemia/lymphoma-2 (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.
Insights
This study explores targeting oral cancer using plant-derived saponin liposomes to deliver anticancer genes. These novel liposomes show potential for selective cancer cell targeting and apoptosis induction, offering an inexpensive therapeutic approach.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Glucocorticoid and Mineralocorticoid receptors influence human cancer development.
- Steroid hormone receptors (SHRs) exhibit aberrant behavior in cancer.
- Targeting SHRs for oral cancer treatment remains underexplored.
Purpose of the Study:
- Investigate SHRs as a potential target for oral cancer therapy.
- Evaluate plant-derived saponin liposomes for targeted drug delivery.
- Assess the efficacy of delivering anticancer genes to oral cancer cells.
Main Methods:
- Formulation of liposomes with synthetic and natural SHR ligands from an Indian medicinal plant.
- Development of lipoplexes for targeted transfection of oral cancer cells.
- Delivery of exogenous p53 gene using saponin-based liposomes to oral squamous cell carcinoma cells.
Main Results:
- Lipoplexes demonstrated targeted transfectability, confirmed by green fluorescent protein expression.
- Saponin-based liposomes successfully delivered the p53 gene, inducing cancer cell apoptosis.
- Apoptosis was mediated by regulating BAX and B-cell leukemia/lymphoma-2 (BCL2) protein levels.
- Efficacy was comparable to synthetic ligand-based delivery systems.
Conclusions:
- Plant saponin-based liposomes offer a promising, inexpensive delivery system for oral cancer treatment.
- These systems exhibit selective targeting of cancer cells, potentially reducing off-target side effects.
- Further development could lead to novel therapeutic strategies for oral cancer.
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