Chemomodulatory Effect of Capsaicin Encapsulated Chitosan Nanoparticles on Lipids, Lipoproteins and Glycoprotein Components in DMBA Induced Mammary Carcinogenesis in Rats
Objectives: Breast cancer is a dreadful public health issue that kills plenty of women all around the world. The peril of breast cancer is strongly linked to lipids, lipoproteins, and glycoproteins. Capsaicin (CAP), a natural alkaloid isolated from chilies, has been reported to possess excellent anti-cancer activity. Unfortunately, the clinical application of this compound is strictly limited due to its low solubility and poor bioavailability. Nanoparticle-based drug delivery systems have set the path for a revolution in cancer therapy by improving its therapeutic value. The aim of the present study was to investigate the effect of CAP encapsulated chitosan nanoparticles (CAP@CS-NP) on lipids, lipoproteins and glycoproteins abnormalities in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis.
Methods: A mammary tumor was induced by a single dose of DMBA 25mg/kg b.wt injected subcutaneously near the mammary gland. The levels of lipid profile, lipoproteins and glycoprotein components were analyzed in the plasma, liver and mammary tissues.
Results: We observed higher levels of total cholesterol (TC), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), hexose, hexosamine and sialic acid in DMBA induced tumor-bearing rats. Moreover, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels were raised and high-density lipoprotein cholesterol (HDL-C) levels were dropped in tumor-bearing rats. The result shows that, CAP@CS-NP 4mg/kg b.wt administration significantly recouped abnormal levels to near-normal levels. It was additionally verified by histological staining in mammary tissues.
Conclusion: Our findings suggest that nanoencapsulation of CAP@CS-NP successfully regulates lipid profile, lipoproteins, and glycoproteins levels.
1.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 2020;71:209–49.
2. Nandakumar N, Rengarajan T, Balamurugan A, Balasubramanian MP. Modulating effects of hesperidin on key carbohydrate-metabolizing enzymes, lipid profile, and membrane-bound adenosine triphosphatases against 7, 12-dimethylbenz (a) anthracene-induced breast carcinogenesis. Hum Exp Toxicol 2014;33:504–16.
3. Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J 2012;279:2610–23.
4. Schulze A, Harris AL. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 2012;491:364– 73.
5. Oliveira-Ferrer L, Legler K, Milde-Langosch K. Role of protein glycosylation in cancer metastasis. Semin Cancer Biol 2017;44:141–52.
6. Periyasamy K, Baskaran K, Ilakkia A, Vanitha K, Selvaraj S, Sakthisekaran D. Antitumor efficacy of tangeretin by targeting the oxidative stress mediated on 7, 12-dimethylbenz (a) anthracene-induced proliferative breast cancer in Sprague– Dawley rats. Cancer Chemother Pharmacol 2015;75:263–72.
7. Hamzehzadeh L, Atkin SL, Majeed M, Butler AE, Sahebkar A. The versatile role of curcumin in cancer prevention and treatment: A focus on PI3K/AKT pathway. J Cell Physiol 2018;233:6530–7.
8. Khorsandi K, Kianmehr Z, Hosseinzadeh R. Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis. Cancer Cell Int 2020;20:18.
9. Chapa-Oliver AM, Mejia-Teniente L. Capsaicin: From plants to a cancer-suppressing agent. Molecules 2016;21:931–9.
10. Park SY, Kim JY, Lee SM, Jun CH, Cho SB, Park CH, et al. Capsaicin induces apoptosis and modulates MAPK signaling in human gastric cancer cells. Mol Med Rep 2014;9:499–502.
11. Friedman JR, Perry HE, Brown KC, Gao Y, Lin J, Stevenson CD, et al. Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway. Biochem Pharmacol 2017;129:54–66.
12. Zhu M, Yu X, Zheng Z, Huang J, Yang X, Shi H. Capsaicin suppressed activity of prostate cancer stem cells by inhibition of Wnt/β‐catenin pathway. Phytother Res 2020;34:817–24.
13. Kalaiyarasi D, Mirunalini S. Capsaicin (Capsicum Annuum): A ubiquitous compound with multivarient pharmaceutical properties. Res J Chem Environ 2021;25:234–40.
14. Singh T, Shukla S, Kumar P, Wahla V, Bajpai VK, Rather IA. Application of nanotechnology in food science: perception and overview. Front Microbiol 2017;8:1–7.
15. Holm BA, Bergey EJ, De T, Rodman DJ, Kapoor R, Levy L, et al. Nanotechnology in biomedical applications. Mol Cryst Liq 2002;374:589–98.
16. Kalaiyarasi D, Manobharathi V, Mirunalini S. Development of nano drugs: A promising avenue for cancer treatment. Res J Biotechnol 2021;16:234–44.
17. Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomed-Nanotechnol 2010;6:153–60.
18. Abd Elgadir M, Uddin MS, Ferdosh S, Adam A, Chowdhury AJ, Sarker MZ. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review. J Food Drug Anal 2015;23:619–29.
19. Arulmozhi V, Pandian K, Mirunalini S. Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB). Colloids Surf B 2013;110:313–20.
20. Chidambaram, N, Baradarajan, A. Influence of selenium on glutathione and some associated enzymes in rats with mammary tumor induced by 7, 12-dimethylbenz (a) anthracene. Mol Cell Biochem 1996;156:101–7.
21. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Asokkumar S, Naveenkumar C, et al. The anti-cancer role of capsaicin in experimentally induced lung carcinogenesis. J Pharmaco punct 2015;18:19–25.
22. Folch J, Lees M, Stanley GS. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957;226:497–509.
23. Zlatkis A, Zak B, Boyle AJ. A new method for the direct determination of serum cholesterol. J Lab Clin Med 1953;41:486–92.
24. Foster LB, Dunn RT. Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method. Clin Chem 1973;19:338–40.
25. Zilversmit DB, Davis AK. Micro determination of plasma phospholipids by trichloroacetic acid precipitation. J Lab Clin Med 1950;35:155–60.
26. Falholt K, Lund B, Falholt W. An easy colorimetric micromethod for routine determination of free fatty acids in plasma. Clin Chim Acta 1973;46:105–11.
27. Wilson DE, Spiger MJ. A dual precipitation method for quantitative plasma lipoprotein measurement without ultracentrifugation. J Lab Clin Med 1973;82:473–82.
28. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.
29. Niebes P. Determination of enzymes and degradation products of glycosaminoglycan metabolism in the serum of healthy and varicose subjects. Clin Chim Acta 1972;42:399– 408.
30. Elson LA, Morgan WT. A colorimetric method for the determination of glucosamine and chondrosamine. Biochem J 1933;27:1824–8.
31. Warren L. The thiobarbituric acid assay of sialic acids. J Biol Chem 1959;234:1971–5.
32. Yamabayashi S. Periodic acid-Schiff-Alcian Blue: A method for the differential staining of glycoproteins. Histochem 1987;19:565–71.
33. Baumann J, Sevinsky C, Conklin DS. Lipid biology of breast cancer. BBA-Mol cell biol 2013;1831:1509–17.
34. Ray G, Husain SA. Role of lipids, lipoproteins and vitamins in women with breast cancer. Clin Biochem 2001;34:71–6.
35. Pattanayak SP, Sunita P, Mazumder PM. Restorative effect of Dendrophthoe falcata (Lf) Ettingsh on lipids, lipoproteins, and lipid-metabolizing enzymes in DMBA-induced mammary gland carcinogenesis in Wistar female rats. Comp Clin Path 2014;23:1013–22.
36. Semb H, Peterson J, Tavernier J, Olivecrona T. Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo. J Biol Chem 1987;262:8390–4.
37. Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J 2012;279:2610–23.
38. Isabella S, Mirunalini S. Protective effect of 3, 3′-Diindolylmethane encapsulated chitosan nanoparticles prop up with lipid metabolism and biotransformation enzymes against possible mammary cancer. J Appl Pharm Sci 2017;7:194–201.
39. Wu Y, Yu X, Yi X, Wu K, Dwabe S, Atefi M, et al. Aberrant phosphorylation of SMAD4 Thr277-mediated USP9x–SMAD4 interaction by free fatty acids promotes breast cancer metastasis. Cancer Res 2017;77:1383–94.
40. Wang Y, Ao X, Vuong H, Konanur M, Miller FR, Goodison S, et al. Membrane glycoproteins associated with breast tumor cell progression identified by a lectin affinity approach. J Proteome Res 2008;7:4313–25.
41. Veena K, Shanthi P, Sachdanandam P. Anti-cancer effect of Kalpaamruthaa on mammary carcinoma in rats with reference to glycoprotein components, lysosomal and marker enzymes. Biol Pharm Bull 2006;29:565–9.
42. Arivazhagan L, Pillai SS. Tangeretin, a citrus pentamethoxyflavone, exerts cytostatic effect via p53/p21 up-regulation and suppresses metastasis in 7, 12-dimethylbenz (α) anthracene-induced rat mammary carcinoma. J Nutr Biochem 2014;25:1140–53.