Abstract
Background: Chemoprevention using natural agents has emerged as a new and promising strategy for reducing cancer burden. Sesamol, a water soluble lignin, is a potent antioxidant with potential anticancer activities. Its small size (molecular weight: 138.34g) coupled with easy permeability (log P: 1.29) results in its excessive systemic loss therefore, compromising local bioavailability. Furthermore, irritant nature of sesamol limits its application on skin per se.
Objective: Present study aims to evaluate chemopreventive efficacy of free and encapsulated (SLNs) sesamol, at gross and molecular level, in DMBA induced skin cancer animal model. Methods: Evaluation is done in terms of tumor burden quantification, histological evaluation of skin, determination of oxidative stress, and quantification of apoptotic proteins, bcl-2 and bax, using both western blot analysis and immunofluorescence studies. Results: Sesamol administration (both in free and encapsulated form) significantly decreased the tumor burden and lipid peroxidation level and increased anti-oxidant levels, thereby hampering the development and promotion of skin tumors. Further, downregulation of bcl-2 and stimulation of bax protein expression on treatment with both free and encapsulated sesamol was responsible for the induction of apoptosis in tumor cells. Encapsulating sesamol into SLNs not only reduced its irritant nature which limits its direct topical application but also improved its local targeting to skin. Conclusion: Both free and encapsulated sesamol demonstrated the inhibition of tumor progression by inducing skin cell apoptosis via bcl-2/bax mediated pathway.Keywords: Chemoprevention, apoptosis, SLNs, antioxidant, apoptotic proteins.
Anti-Cancer Agents in Medicinal Chemistry
Title:Sesamol Induces Apoptosis by Altering Expression of Bcl-2 and Bax Proteins and Modifies Skin Tumor Development in Balb/c Mice
Volume: 17 Issue: 5
Author(s): Rishi Bhardwaj, SN Sanyal, Kim Vaiphei, Vandita Kakkar, Parneet Kaur Deol, Indu Pal Kaur*Tranum Kaur*
Affiliation:
- University Institute of Pharmaceutical Sciences, UGC Centre for Advance Study, Panjab University, Chandigarh-160014,India
- Department of Chemistry and Biochemistry, University of Windsor, Windsor, N9B 3P4 ON,Canada
Keywords: Chemoprevention, apoptosis, SLNs, antioxidant, apoptotic proteins.
Abstract: Background: Chemoprevention using natural agents has emerged as a new and promising strategy for reducing cancer burden. Sesamol, a water soluble lignin, is a potent antioxidant with potential anticancer activities. Its small size (molecular weight: 138.34g) coupled with easy permeability (log P: 1.29) results in its excessive systemic loss therefore, compromising local bioavailability. Furthermore, irritant nature of sesamol limits its application on skin per se.
Objective: Present study aims to evaluate chemopreventive efficacy of free and encapsulated (SLNs) sesamol, at gross and molecular level, in DMBA induced skin cancer animal model. Methods: Evaluation is done in terms of tumor burden quantification, histological evaluation of skin, determination of oxidative stress, and quantification of apoptotic proteins, bcl-2 and bax, using both western blot analysis and immunofluorescence studies. Results: Sesamol administration (both in free and encapsulated form) significantly decreased the tumor burden and lipid peroxidation level and increased anti-oxidant levels, thereby hampering the development and promotion of skin tumors. Further, downregulation of bcl-2 and stimulation of bax protein expression on treatment with both free and encapsulated sesamol was responsible for the induction of apoptosis in tumor cells. Encapsulating sesamol into SLNs not only reduced its irritant nature which limits its direct topical application but also improved its local targeting to skin. Conclusion: Both free and encapsulated sesamol demonstrated the inhibition of tumor progression by inducing skin cell apoptosis via bcl-2/bax mediated pathway.Export Options
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Cite this article as:
Bhardwaj Rishi, Sanyal SN, Vaiphei Kim, Kakkar Vandita, Deol Kaur Parneet, Kaur Pal Indu*, Kaur Tranum*, Sesamol Induces Apoptosis by Altering Expression of Bcl-2 and Bax Proteins and Modifies Skin Tumor Development in Balb/c Mice, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (5) . https://dx.doi.org/10.2174/1871520616666160819103249
DOI https://dx.doi.org/10.2174/1871520616666160819103249 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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