Does Bromelain-Cisplatin Combination Afford In-Vitro Synergistic Anticancer Effects on Human Prostatic Carcinoma Cell Line, PC3?
AbstractBackground: Bromelain enhances anticancer impacts to chemotherapeutic agents. The question as to whether bromelain does promote in-vitro cytotoxic and proapoptotic effects of cisplatin on human prostatic carcinoma PC3 cell line was investigated. Materials and Methods: PC3 (human prostatic carcinoma) cells were treated either single or in combination with bromelain and/or cisplatin. MTT, clonogenic assay, flow cytometry and real-time quantitative polymerase chain reaction were used to investigate cell viability, colony formation, proapoptotic potential and p53 gene expression, respectively. Results: Cisplatin (IC10) combined with bromelain (IC40) significantly affected PC3 cell viability, inhibited colony formation, as well increased p53 proapoptotic gene expression compared to cisplatin single treatment. Nevertheless, bromelain-cisplatin chemoherbal combination did not display any additive proapoptotic effect compared to single treatments. Conclusion: Bromelain-cisplatin chemoherbal combination demonstrated synergistic in-vitro anticancer effect on human prostatic carcinoma cell line, PC3, that drastically reduced required cisplatin dose. [GMJ.2020;9:e1749]
Ahel J, Hudorović N, Višnja Vičić-Hudorović C, Nikles H. TGF-BETA in the natural history of prostate cancer. Acta Clin Croat. 2019;58(1):128-38.
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(6):252-71.
Campana LG, Edhemovic I, Soden D, Perrone AM, Scarpa M, Campanacci L, et al. Electrochemotherapy-Emerging applications technical advances, new indications, combined approaches, and multi-institutional collaboration. Eur J Surg Oncol. 2019;45(2):92-102.
Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 2019;88:102925.
Damia G, Broggini M. Platinum Resistance in Ovarian Cancer: Role of DNA Repair. Cancers (Basel). 2019;11(1):119.
Sun W, Sanderson PE, Zheng W. Drug combination therapy increases successful drug repositioning. Drug Discov Today. 2016;21(7):1189-95.
Lin SR, Chang CH, Hsu CF, Tsai MJ, Cheng H, Leong MK, et al. Natural compounds as potential adjuvants to cancer therapy: preclinical evidence. Br J Pharmacol. 2019;177(6):1409-23.
Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep. 2016;5(3):283-8.
Soheilifar S, Bidgoli M, Hooshyarfard A, Shahbazi A, Vahdatinia F, Khoshkhooie F. Effect of Oral Bromelain on Wound Healing, Pain, and Bleeding at Donor Site Following Free Gingival Grafting: A Clinical Trial. J Dent (Tehran). 2018;15(5):309-16.
Amini A, Masoumi-Moghaddam S, Ehteda A, Liauw W, Morris DL. Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells. Am J Cancer Res. 2016;6(2):350-69.
Tysnes BB, Maurer HR, Porwol T, Probst B, Bjerkvig R, Hoover F. Bromelain reversibly inhibits invasive properties of glioma cells. Neoplasia. 2001;3(6):469-79.
Pauzi AZ, Yeap SK, Abu N, Lim KL, Omar AR, Aziz SA, et al. Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro. Chin Med. 2016;11:46.
Satari A, Amini AS, Raeisi E, Lemoigne Y, Hiedarian E. Synergetic impact of combined 5-fluorouracil and rutin on apoptosis in pc3 cancer cells through the modulation of p53 gene expression. Adv Pharm Bull. 2019;9(3):462-9.
Raeisi F, Shahbazi-Gahrouei D, Raeisi E, Heidarian E. Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4T1 breast cancer cells. J Med Signals Sens. 2019;9(1):68-74.
Groeben C, Wirth MP. Prostate cancer: Basics on clinical appearance, diagnostics and treatment. Med Monatsschr Pharm. 2017;40(5):192-201.
Kalra N, Bhui K, Roy P, Srivastava S, George J, Prasad S, et al. Regulation of p53,nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. Toxicol Appl Pharmacol. 2008;226(1):30-7.
Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol. 2005;205(2):275-92.
Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans. 2018;47(19):6645-53.
Hoseinzadeh S, Raeisi E, Lemoigne Y, Heidarian E. Effects of combined 5-Fluorouracil and ZnO NPs on human breast cancer MCF-7 Cells: P53 gene expression, Bcl-2 signaling pathway, and invasion activity. Nanomed J. 2019;6(3):232-40.
Wei Y, Yang P, Cao S, Zhao L. The combination of curcumin and 5-fluorouracil in cancer therapy. Arch Pharm Res. 2018;41(1):1-13.
Alaufi OM, Noorwali A, Zahran F, Al-Abd AM, Al-Attas S. Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro. Sci Rep. 2017;17(1):13131.
Chobotova K, Vernallis A, Majid FA. Bromelain's activity and potential as an anti-cancer agent: Current evidence and perspectives. Cancer Lett. 2010;290(2):148-56.
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. Eur J Pharm Biopharm. 2015;91:35-46.
Secor ER Jr, Szczepanek SM, Castater CA, Adami AJ, Matson AP, Rafti ET, et al. Bromelain inhibits allergic sensitization and murine asthma via modulation of dendritic cells. Evid Based Complement Alternat Med. 2013;2013:702196.
Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol. 2008;128(1):66-74.
Ghensi P, Cucchi A, Bonaccorso A, Ferroni L, Gardin C, Mortellaro C, et al. In vitro effect of bromelain on the regenerative properties of mesenchymal stem cells. J Craniofac Surg. 2019;30(4):1064-7.
Chang TC, Wei PL, Makondi PT, Chen WT, Huang CY, Chang YJ. Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy. PLoS One. 2019;14(1):e0210274.
Baez R, Lopes MT, Salas CE, Hernandez M. In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. Planta Med. 2007;73(13):1377-83.
Dhandayuthapani S, Perez HD, Paroulek A, Chinnakkannu P, Kandalam U, Jaffe M, et al. Bromelain-induced apoptosis in GI-101A breast cancer cells. J Med Food. 2012;15(4):344-9.
Gläser D, Hilberg T. The influence of bromelain on platelet count and platelet activity in vitro. Platelets. 2006;17(1):37-41.
Amini A, Ehteda A, Masoumi Moghaddam S, Akhter J, Pillai K, Morris DL. Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). Onco Targets Ther. 2013;6:403-9.
Pillai K, Ehteda A, Akhter J, Chua TC, Morris DL. Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells. Anticancer Drugs. 2014;25(2):150-60.
Nasiri R, Almaki JH, Idris A, Nasiri M, Irfan M, Majid FA. Targeted delivery of bromelain using dual mode nanoparticles: Synthesis, physicochemical characterization, in vitro and in vivo evaluation. RSC Adv. 2017;7:40074‑94.
Bendale Y, Bendale V, Paul S. Evaluation of cytotoxic activity of platinum nanoparticles against normal and cancer cells and its anticancer potential through induction of apoptosis. Integr Med Res. 2017;6(2):141-8.
Bhui K, Prasad S, George J, Shukla Y. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett. 2009;282(2):167-76.
Amini A, Masoumi-Moghaddam S, Ehteda A, Morris DL. Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy. J Exp Clin Cancer Res. 2014;33(1):92.
Chaudhary B, Bist R. Protective manifestation of bacoside A and bromelain in terms of cholinesterases, gamma-amino butyric acid, serotonin level and stress proteins in the brain of dichlorvos-intoxicated mice. Cell Stress Chaperones. 2017;22(3):371-6.
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