Physicochemical Properties of Bromelain Adsorption on Magnetic Carbon Nanoparticles and in Vitro Cytotoxicity on Breast Cancer Cells

Keywords: Bromelain enzyme, Anticarcinogenic, Magnetic carbon nanoparticles, Breast cancer

Abstract

Background and Aim: As a proteolytic enzyme extracted from the pineapple stalk, Bromelain (Br) is known as an anticancer agent. In the first stage of this research, we studied the physicochemical factors which influence the maximum adsorption of Br on magnetic carbone nanoparticles (MCNPs) and then the anticarcinogenic activity of Br enzyme alone. Moreover, they were evaluated in combination with these particles on MCF-7 breast cancer cells. Materials and Methods: The operational determinants influencing Br adsorption such as pH, contact time (30, 60, 90, 120 and 180 min), adsorbent dosage (1 gr/L, 5 gr/L), initial Br concentration (50, 150 and 300 mg/L) and temperature (35 and 50°C) were studied in detail. Then cancer cells were exposed to various Br concentrations (0.1 μg/mL, 1 μg/mL, 10 μg/mL, and 100 μg/mL) and the cell viability was determined by methylthiazol tetrazolium (MTT) assay after 24, 48 and 72 h. Results: The highest adsorption of Br on MCNPs was 44 mg/g and was achieved at pH 5, 35°C and 120 min with 50 mg/L initial Br concentration and 1g/L MCNPs. The adsorption used the Freundlich and pseudo first-order kinetic models. The results indicated that MCNPs could be a potential effective adsorbent for the removal of Br. MTT assay indicated that a 100 μg/mL concentration of Br alone (after 24 h) and in combination with MCNPs (after 72 h) could efficiently inhibit the MCF-7 breast cancer cells. Conclusion: Although the dose of Bromelain on synthesized MCNPS is about 440 times less than Bromelain alone, it possesses a significant cytotoxicity (P<0.001). Moreover, synthesized MCNPS had a considerable advantage of slow delivery which is favorable for the treatment of cancer.

Author Biography

Mina Ramezani*, Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
Biology

References

da Costa Vieira RA, Biller G, Uemura G, Ruiz CA, Curado MP. Breast cancer screening in developing countries. Clinics. 2017;72(4):244-53.

Luo C, Sun J, Sun B, He Z. Prodrug-based nanoparticulate drug delivery strategies for cancer therapy. Trends in pharmacological sciences. 2014; 1;35(11):556-66.

Tran N, Webster TJ. Magnetic nanoparticles: biomedical applications and challenges. Journal of Materials Chemistry. 2010;20(40):8760-7.

Denkbaş EB, Çelik E, Erdal E, Kavaz D, Akbal Ö, Kara G, et al. Magnetically based nanocarriers in drug delivery. InNanobiomaterials in drug delivery 2016; 1 (pp. 285-331). William Andrew Publishing.

Giouroudi I, Kosel J. Recent progress in biomedical applications of magnetic nanoparticles. Recent patents on nanotechnology. 2010; 1;4(2):111-8.

Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. Journal of ethnopharmacology. 1988;22(2):191-203.

Bala M, Ismail NA, Mel M, Jami MS, Salleh HM, Amid A. Bromelain production: current trends and perspective. Archives Des Sciences. 2012;65(11):369-99.

Gani MB, Nasiri R, Almaki JH, Majid FA, Marvibaigi M, Amini N, et al. In vitro antiproliferative activity of fresh pineapple juices on ovarian and colon cancer cell lines. International Journal of Peptide Research and Therapeutics. 2015;21(3):353-64.

Mamo J, Assefa F. Antibacterial and Anticancer Property of Bromelain: A Plant Protease Enzyme from Pineapples (Ananas comosus). Current trends in Biomedical Engineering and Biosciences. 2019;19(2):60-8.

Tochi BN, Wang Z, Xu SY, Zhang W. Therapeutic application of pineapple protease (bromelain): a review. Pakistan journal of nutrition. 2008;7(4):513-20.

Castell JV, Friedrich GE, Kuhn CS, Poppe GE. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. American Journal of Physiology-Gastrointestinal and Liver Physiology. 1997;273(1):G139-46.

Chobotova K, Vernallis AB, Majid FA. Bromelain’s activity and potential as an anti-cancer agent: current evidence and perspectives. Cancer letters. 2010;290(2):148-56.

Bhui K, Tyagi S, Srivastava AK, Singh M, Roy P, Singh R, et al. Bromelain inhibits nuclear factor kappa‐B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis. Molecular carcinogenesis. 2012;51(3):231-43.

Paroulek AF, Jaffe M, Rathinavelu A. The effects of the herbal enzyme bromelain against breast cancer cell line GI-101A (Doctoral dissertation, Nova Southeastern University).

Amini A, Ehteda A, Moghaddam SM, Akhter J, Pillai K, Morris DL. Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). OncoTargets and therapy. 2013;6:403.

Lee JH, Lee JT, Park HR, Kim JB. The potential use of bromelain as a natural oral medicine having anticarcinogenic activities. Food science & nutrition. 2019;7(5):1656-67.

Nasiri R, Almaki JH, Idris A, Nasiri M, Irfan M, Majid FA, et al. Targeted delivery of bromelain using dual mode nanoparticles: synthesis, physicochemical characterization, in vitro and in vivo evaluation. RSC advances. 2017;7(64):40074-94.

Liu Z, Qi Y, Lu C. High efficient ultraviolet photocatalytic activity of BiFeO 3 nanoparticles synthesized by a chemical coprecipitation process. Journal of Materials Science: Materials in Electronics. 2010;21(4):380-4.

Kakavandi B, Esrafili A, Mohseni-Bandpi A, Jonidi Jafari A, Rezaei Kalantary R. Magnetic Fe3O4@ C nanoparticles as adsorbents for removal of amoxicillin from aqueous solution. Water science and technology. 2014;69(1):147-55.

Ho YS, McKay G. Pseudo-second order model for sorption processes. Process biochemistry. 1999;34(5):451-65.

Ai L, Zhou Y, Jiang J. Removal of methylene blue from aqueous solution by montmorillonite/CoFe2O4 composite with magnetic separation performance. Desalination. 2011;266(1-3):72-7.

Naghizadeh A, Nasseri S, Rashidi AM, Rezaei Kalantary R, Nabizadeh R, Mahvi AH. Adsorption kinetics and thermodynamics of hydrophobic natural organic matter (NOM) removal from aqueous solution by multi-wall carbon nanotubes. Water Science and Technology: Water Supply. 2013;13(2):273-85.

Arshad ZI, Amid A, Yusof F, Jaswir I, Ahmad K, Loke SP. Bromelain: an overview of industrial application and purification strategies. Applied microbiology and biotechnology. 2014;98(17):7283-97

Omidvar M, mahmoud Mousavi S, Soltanieh M, Safekordi AA. Preparation and characterization of poly (ethersulfone) nanofiltration membranes for amoxicillin removal from contaminated water. Journal of Environmental Health Science and Engineering. 2014;12(1):18.

Chen H, Ma X, Li Z, Shi Q, Zheng W, Liu Y, et al. Functionalization of single-walled carbon nanotubes enables efficient intracellular delivery of siRNA targeting MDM2 to inhibit breast cancer cells growth. Biomedicine & Pharmacotherapy. 2012;66(5):334-8.

Jha I, Venkatesu P. Deciphering the interactions of bromelain with carbon nanotubes: role of protein as well as carboxylated multiwalled carbon nanotubes in a complexation mechanism. The Journal of Physical Chemistry C. 2016;120(28):15436-45.

Bhatnagar P, Pant AB, Shukla Y, Chaudhari B, Kumar P, Gupta KC. Bromelain nanoparticles protect against 7, 12-dimethylbenz [a] anthracene induced skin carcinogenesis in mouse model. European Journal of Pharmaceutics and Biopharmaceutics. 2015;91:35-46.

Bhatnagar P, Pant AB, Shukla Y, Panda A, Gupta KC. Hyaluronic acid grafted PLGA copolymer nanoparticles enhance the targeted delivery of Bromelain in Ehrlich’s Ascites Carcinoma. European Journal of Pharmaceutics and Biopharmaceutics. 2016;105:176-92.

Wei B, He L, Wang X, Yan GQ, Wang J, Tang R. Bromelain-decorated hybrid nanoparticles based on lactobionic acid-conjugated chitosan for in vitro anti-tumor study. Journal of Biomaterials Applications. 2017;32(2):206-18.

Published
2021-11-19
Section
Original Article