THERAPEUTIC PROFILING OF NANO ENCAPSULATED DIOSGENIN VIA ATTENUATING HORMONAL STATUS, CELL PROLIFERATION, INFLAMMATORY RESPONSES, AND APOPTOSIS IN AN ANIMAL MODEL OF MAMMARY ONCOGENESIS

Authors

  • MANOBHARATHI VENGAIMARAN Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India
  • KALAIYARASI DHAMODHARAN Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India
  • MIRUNALINI SANKARAN Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India

DOI:

https://doi.org/10.22159/ijap.2021v13i6.42777

Keywords:

Diosgenin, Mammary carcinogenesis, Hormonal status, Cell proliferation, Apoptosis, Molecular docking.

Abstract

Objective: The central motive of this study is to explore the therapeutic impact of Diosgenin encapsulated Chitosan nanoparticles (DG@CS-NP) on mammary carcinogenesis in female Sprague Dawley rats via modulating hormonal status, cell proliferation, inflammatory responses, and Apoptosis.

Methods: 7,12-dimethylbenz(a)anthracene (DMBA) was administered subcutaneously near the mammary gland (25mg/kg b.wt) to provoke mammary tumor in female Sprague Dawley rats. Following the progress of a tumor, DMBA-induced tumor-bearing rats were medicated orally with 5 mg/kg b.wt of DG@CS-NP. Consequently, the expression of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, Bcl-2, Caspases-3, and p53 in experimental rats were revealed via architectural immunohistochemistry. Further, Diosgenin interactions with these proteins were evidently confirmed by molecular docking analysis.

Results: As a result, we noticed diminished levels of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, and Bcl-2 expressions in DG@CS-NP medicated rats as well as with elevated levels of Caspases-3 and p53 expressions. In DMBA rats, the expressions were vice versa. Additionally, molecular docking analyses support these outcomes by highlighting the strong interaction between Diosgenin and breast cancer targets.

Conclusion: These reports prove that DG@CS-NP imposes its therapeutic impact by hormonal adjustments, downregulating proteins involved in inflammation and cellular proliferation, and thereby promotes apoptosis by impeding apoptotic inhibitors.

Downloads

Download data is not yet available.

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71:209-49.

Manobharathi V, Kalaiyarasi D, Mirunalini S. A concise critique on Breast Cancer: A historical and scientific perspective. Res J Biotechnol 2021; 16:220-30.

Pérez-Soto E, Estanislao-Gómez CC, Pérez-Ishiwara DG, Ramirez-Celis C, del Consuelo Gómez-García M. Cytotoxic Effect and Mechanisms from Some Plant-Derived Compounds in Breast Cancer. Cytotoxicity-Definition, Identification, and Cytotoxic Compounds 2019;6:1-24.

Korsh J, Shen A, Aliano K, Davenport T. Polycyclic aromatic hydrocarbons and breast cancer: a review of the literature. Breast Care 2015; 10:316-8.

Vinothini G, Murugan RS, Nagini S. Evaluation of molecular markers in a rat model of mammary carcinogenesis. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 2009; 17:483-93.

Karimi B, Ashrafi M, Shomali T, Yektaseresht A. Therapeutic effect of simvastatin on DMBA‐induced breast cancer in mice. Fundam Clin Pharmacol 2019; 33:84-93.

Port Louis LR, Varshney KC, Nair MG. An immunohistochemical study on the expression of sex steroid receptors in canine mammary tumors. Int Sch Res Notices 2012; 1:1-7.

Alvarado A, Lopes AC, Faustino-Rocha AI, Cabrita AM, Ferreira R, Oliveira PA, et al. Prognostic factors in MNU and DMBA-induced mammary tumors in female rats. Pathol Res Pract 2017; 213:441-6.

Vinothkumar V, Manoharan S, Sindhu G, Nirmal MR, Vetrichelvi V. Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7, 12-dimethylbenz [a] anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 2012; 369:17-25.

Lengare PV, Khandeparkar SG, Joshi AR, Gogate BP, Solanke SG, Gore SH. Immunohistochemical expression of cyclin D1 in invasive breast carcinoma and its correlation with clinicopathological parameters. Indian J Pathol Microbiol 2020; 63:376-81.

Wang W, Nag SA, Zhang R. Targeting the NFκB signaling pathways for breast cancer prevention and therapy. Curr Med Chem 2015; 22:264-89.

Zhou XL, Fan W, Yang G, Yu MX. The clinical significance of PR, ER, NF-κB, and TNF-α in breast cancer. Dis Markers 2014; 1:1-7.

Luo JL, Kamata H, Karin M. IKK/NF-κB signaling: balancing life and death–a new approach to cancer therapy. J Clin Invest. 2005; 115:2625-32.

Purushothaman A, Nandhakumar E, Shanthi P, Sachidanandam TP. Antiproliferative and apoptotic effects of Shemamruthaa, a herbal preparation, in 7, 12-dimethylbenz (a) anthracene-induced breast cancer rats. Evid-Based Compl Alt Med 2015; 20:259-68.

Mitra S, Dash R. Natural products for the management and prevention of breast cancer. Evid-Based Compl Alt Med 2018; 1:1-23.

Xu XH, Li T, Fong CM, Chen X, Chen XJ, Wang YT, et al. Saponins from Chinese medicines as anticancer agents. Molecules 2016; 21:1-27.

Manobharathi V, Mirunalini S. Pharmacological characteristics of a phyto steroidal food saponin: Diosgenin. Afr J Biol Sci 2020; 2:77-87.

Arulmozhi V, Pandian K, Mirunalini S. Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB). Colloid Surf B 2013; 110:313-20.

Isabella S, Mirunalini S, Pandiyan K. 3, 3′-Diindolylmethane encapsulated chitosan nanoparticles accelerates inflammatory markers, ER/PR, glycoprotein and mast cells population during chemical carcinogen induced mammary cancer in rats. Indian J Clin Biochem 2018; 33:397-405.

Jagadeesan J, Nandakumar N, Rengarajan T, Balasubramanian MP. Diosgenin, a steroidal saponin, exhibits anticancer activity by attenuating lipid peroxidation via enhancing antioxidant defense system during NMU-induced breast carcinoma. J Environ Pathol Toxicol Oncol 2012; 31:121-9.

Kumar BP, Puvvada N, Rajput S, Sarkar S, Das SK, Emdad L, et al. Sequential release of drugs from hollow manganese ferrite nanocarriers for breast cancer therapy. J. Mater. Chem. B. 2015; 3:90-101.

Isabella S, Mirunalini S. 3, 3′-Diindolylmethane-encapsulated chitosan nanoparticles accelerate molecular events during chemical carcinogen-induced mammary cancer in Sprague Dawley rats. Breast Cancer 2019; 26:499-509.

Morris GM, Goodsell DS, Pique ME, Lindstrom WL, Huey R, Forli S, et al. AutoDock 4.2 user guide: The Scripps Research Institute; 2009;1-66.

Younas M, Hano C, Giglioli-Guivarc'h N, Abbasi BH. Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives. RSC Adv 2018; 8:29714-44.

Sethi G, Shanmugam MK, Warrier S, Merarchi M, Arfuso F, Kumar AP, et al. Pro-apoptotic and anti-cancer properties of diosgenin: a comprehensive and critical review. Nutrients 2018; 10:1-12.

Kalaiyarasi D, Manobharathi V, Mirunalini S. Development of nano drugs: A promising avenue for cancer treatment. Res J Biotechnol 2021;16;234-44.

Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Molecules 2015; 20:13384-421.

Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I κ B kinase activation and NF-κ B-regulated gene expression. Oncogene 2006; 25:1463-73.

Thangarasu R, Pachaiappan P, Subbaiyan T. Anti-Estrogenic and Anti-Cell Proliferative Effect of Allyl Isothiocyanate in Chemoprevention of Chemically Induced Mammary Carcinogenesis in Rats. Pathol Oncol Res 2020; 26:913-25.

Tang P, Tse GM. Immunohistochemical surrogates for molecular classification of breast carcinoma: a 2015 update. Arch Pathol Lab Med 2016; 140:806-14.

Beresford MJ, Wilson GD, Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res 2006; 8:1-11.

Martins GR, Gelaleti GB, Moschetta MG, Maschio-Signorini LB, Zuccari DA, de Campos P. Proinflammatory and anti-inflammatory cytokines mediated by NF-κB factor as prognostic markers in mammary tumors. Mediators Inflamm 2016; 1:1-10.

Kumaraguruparan R, Prathiba D, Nagini S. Of humans and canines: immunohistochemical analysis of PCNA, Bcl-2, p53, cytokeratin and ER in mammary tumours. Res Vet Sci 2006; 81:218-24.

Published

26-08-2021

How to Cite

VENGAIMARAN, M., DHAMODHARAN, K., & SANKARAN, M. (2021). THERAPEUTIC PROFILING OF NANO ENCAPSULATED DIOSGENIN VIA ATTENUATING HORMONAL STATUS, CELL PROLIFERATION, INFLAMMATORY RESPONSES, AND APOPTOSIS IN AN ANIMAL MODEL OF MAMMARY ONCOGENESIS. International Journal of Applied Pharmaceutics, 13(6). https://doi.org/10.22159/ijap.2021v13i6.42777

Issue

Section

Original Article(s)