Skip to main content
SpringerLink
Log in

Cytotoxic Effect of Bromelain on HepG2 Hepatocellular Carcinoma Cell Line

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Cancer is a complicated long-term disease due to computable key molecular players involved in aggravating the disease. Among various kinds of cancer, hepatocellular carcinoma (HCC) is the ninth leading cause of cancer. Recently, plant-based products are gaining a lot of attention in the field of research because of their anti-tumor properties. In our previous study, we reported based on in-silico method that bromelain, a cysteine protease extracted from the stem of the pineapple, has high binding affinity with the transcription factors p53 and β-catenin proteins which are key players in controlling the progression of hepatocellular carcinoma. Bromelain, isolated mainly from the stem of Pineapple (Ananas comosus), belongs to the family Bromeliaceae. The present study deals with preclinical analysis of bromelain as an anti-cancer agent and its intracellular effect on the expression of p53 and β-catenin protein. Our study reports cytotoxic activity, cell proliferation, migration, invasion, arrest in the S-phase, and G2/M phase in cell cycle analysis by treating with bromelain in HepG2 cell lines. We also report up-regulation of p53 protein by drug-induced impediment leading to apoptotic process in HepG2 cells and down-regulation of β-catenin protein in HepG2 cells which interferes in β-catenin/TCF-DNA interaction further, down-regulating Wnt genes and suppressing the canonical pathway. Finally, we conclude that bromelain inhibits tumorigenic potential in HepG2 cell lines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

The data generated during the study are available from the corresponding author on reasonable request.

References

  1. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  2. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65(1–2), 55–63. https://doi.org/10.1016/0022-1759(83)90303-4.

    Article  CAS  PubMed  Google Scholar 

  3. Liang, C. C., Park, A. Y., & Guan, J. L. (2007). In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nature Protocols, 2(2), 329–333. https://doi.org/10.1038/nprot.2007.30.

    Article  CAS  PubMed  Google Scholar 

  4. Boyden, S. (1962). The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. Journal of Experimental Medicine, 115, 453–466. https://doi.org/10.1084/jem.115.3.453.

    Article  CAS  Google Scholar 

  5. Woolston, C., & Martin, S. (2011). Analysis of tumor and endothelial cell viability and survival using sulforhodamine B and clonogenic assays. Methods in Molecular Biology, 740, 45–56. https://doi.org/10.1007/978-1-61779-108-6_7.

    Article  CAS  PubMed  Google Scholar 

  6. Murphy, M. P. (2009). How mitochondria produce reactive oxygen species. The Biochemical Journal, 417(1), 1–13. https://doi.org/10.1042/bj20081386.

    Article  CAS  PubMed  Google Scholar 

  7. Halliwell, B., & Gutteridge, J. (1989). Free radicals in biology and medicine (5th ed.). Oxford: Clarendon Press

    Google Scholar 

  8. Das, U. N. (2002). A radical approach to cancer. Medical Science Monitor,, 8(4), 79–82

    Google Scholar 

  9. Galeotti, T., Borrello, S., & Masotti, L. (1990). Oxy-radical sources, scavenger systems and membrane damage in cancer cells. In D. K. Das (Ed.), Oxygen radicals: Systemic events and disease processes (pp. 129–148). Basel: Karger

    Chapter  Google Scholar 

  10. Yu, B. P. (1994). Cellular defenses against damage from reactive oxygen species. Physiological Reviews, 74(1), 139–162. https://doi.org/10.1152/physrev.1994.74.1.139.

    Article  CAS  PubMed  Google Scholar 

  11. Latchman, D. S. (1997). Transcription factors: an overview. The International Journal of Biochemistry & Cell Biology, 29(12), 1305–1312. https://doi.org/10.1016/S1357-2725(97)00085-X.

    Article  CAS  Google Scholar 

  12. Malz, M., Pinna, F., Schirmacher, P., & Breuhahn, K. (2012). Transcriptional regulators in hepatocarcinogenesis — key integrators of malignant transformation. Journal of Hepatology, 57(1), 186–195. https://doi.org/10.1016/j.jhep.2011.11.029.

    Article  CAS  PubMed  Google Scholar 

  13. Boyault, S., Rickman, D. S., de Reynies, A., Balabaud, C., Rebouissou, S., & Jeannot, E. (2007). Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology, 45(1), 42–52. https://doi.org/10.1002/hep.21467.

    Article  CAS  PubMed  Google Scholar 

  14. Hoshida, Y., Nijman, S. M., Kobayashi, M., Chan, J. A., Brunet, J. P., Chiang, D. Y., et al. (2009). Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Research, 69(18), 7385–7392. https://doi.org/10.1158/0008-5472.CAN-09-1089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lee, J. S., Chu, I. S., Heo, J., Calvisi, D. F., Sun, Z., Roskams, T., et al. (2004). Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology, 40, 667–676. https://doi.org/10.1002/hep.20375.

    Article  CAS  PubMed  Google Scholar 

  16. Moinzadeh, P., Breuhahn, K., Stutzer, H., & Schirmacher, P. (2005). Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade — results of an explorative CGH meta-analysis. British Journal of Cancer, 92(5), 935–941. https://doi.org/10.1038/sj.bjc.6602448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Feitelson, M. A., & Duan, L. X. (1997). Hepatitis B virus X antigen in the pathogenesis of chronic infections and the development of hepatocellular carcinoma. American Journal of Pathology, 150(4), 1141–1157

    CAS  Google Scholar 

  18. Lasky, T., & Magder, L. (1997). Hepatocellular carcinoma p53 G > T transversions at codon 249: the fingerprint of aflatoxin exposure? Environmental Health Perspectives, 105(4), 392–397. https://doi.org/10.1289/ehp.97105392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ozturk, M. (1991). P53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet, 338(8779), 1356–1359. https://doi.org/10.1016/0140-6736(91)92236-U.

    Article  CAS  PubMed  Google Scholar 

  20. Wang, M., Xi, D., & Ning, Q. (2017). Virus-induced hepatocellular carcinoma with special emphasis on HBV. Hepatology International, 11(2), 171–180. https://doi.org/10.1007/s12072-016-9779-5.

    Article  PubMed  Google Scholar 

  21. Rathnavelu, V., Alitheen, N., Sohila, S., Kanagesan, S., & Ramesh, R. (2016). Potential role of bromelain in clinical and therapeutic applications. Biomedical Reports, 5(3), 283–288. https://doi.org/10.3892/br.2016.720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hale, L. P., Greer, P. K., Trinh, C. T., & James, C. L. (2005). Proteinase activity and stability of natural bromelain preparations. IntImmunopharmacol, 5(4), 783–793. https://doi.org/10.1016/j.intimp.2004.12.007.

    Article  CAS  Google Scholar 

  23. Wu, W., Ng, H. S., Sun, I., & Lan, J. C. (2017). Single step purification of bromelain from Ananascomosus pulp using a polymer/salt aqueous biphasic system. Journal of Taiwan Institute of Chemical Engineers, 79, 158–162

    Article  CAS  Google Scholar 

  24. Barth, H., Guseo, A., & Klein, R. (2005). In vitro study on the immunological effect of bromelain and trypsin on mononuclear cells from humans. European Journal of Medical Research, 10(8), 325–331

    CAS  PubMed  Google Scholar 

  25. Gutfreund, A. E., Taussig, S. J., & Morris, A. K. (1978). Effect of oral bromelain on blood pressure and heart rate of hypertensive patients. Hawaii Medical Journal, 37(5), 143–146

    CAS  PubMed  Google Scholar 

  26. Chang, T. C., Wei, P. L., Makondi, P. T., Chen, W. T., Huang, C. Y., & Chang, Y. J. (2019). Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy. PLoS One, 14(1), eo210274. https://doi.org/10.1371/journal.pone.0210274.

    Article  CAS  Google Scholar 

  27. Murthy, S. S., & Bala Narasiaha, T. (2019). Molecular docking studies of phytocompounds with transcriptional factors in hepatocellular carcinoma. RJC, 14(4), 2030–2038. https://doi.org/10.31788/RJC.2019.1245475.

    Article  Google Scholar 

  28. Wilson, A. P. (2000). Cytotoxicity and viability assays in animal cell culture: A practical approach (3rd ed.). Oxford: Oxford University Press, UK

    Google Scholar 

  29. Kumar, A., Jagadeeshan, S., Pitani, R., Ramshankar, V., Venkitasamy, K., Venkatraman, G., & Rayala, S. (2016). Snail-modulated microRNA 493 forms a negative feedback loop with the insulin-like growth factor 1 receptor pathway and blocks tumorigenesis. Molecular And Cellular Biology, 37(6). https://doi.org/10.1128/mcb.00510-16.

  30. Cell Cycle Analysis by Propidium Iodide Staining: Flow Cytometry Core Facility, Camelia Botnar Laboratories, Room P3.016 UCL Institute of Child Health. 30 Guilford Street, London

  31. Sun, M., & Zigman, S. (1978). An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Analytical Biochemistry, 90(1), 81–89. https://doi.org/10.1016/0003-2697(78)90010-6.

    Article  CAS  PubMed  Google Scholar 

  32. Aebi, H. (1984). Catalase in vitro. Oxygen Radicals in Biological Systems, 13, 121–126. https://doi.org/10.1016/S0076-6879(84)05016-3.

    Article  Google Scholar 

  33. Moron, M. A., Depierre, J. W., & Manner, V. B. (1979). Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat liver. Biochimica et Biophysica Acta, 582, 67–68

    Article  CAS  PubMed  Google Scholar 

  34. Hogberg, J., Larsen, E. R., Kristogerson, A., & Ovrhenius, S. (1974). NADPH-dependent reductase solubilised from microsomes of peroxidation and its activity. Biochemical and Biophysical Research Communications, 56, 836

    Article  CAS  PubMed  Google Scholar 

  35. Chang, H., Huang, H., Huang, T., Yang, P., Wang, Y., & Juan, H. (2013). Flow cytometric detection of reactive oxygen species. Bio-protocol, 3(8), e431. https://doi.org/10.21769/BioProtoc.431.

    Article  Google Scholar 

  36. Jagadeeshan, S., Subramanian, A., Tentu, S., Beesetti, S., Singhal, M., Raghavan, S., et al. (2016). P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer. Annals of Oncology, 27(8), 1546–1556. https://doi.org/10.1093/annonc/mdw184.

    Article  CAS  PubMed  Google Scholar 

  37. Amini, A., Ehteda, A., MasoumiMoghaddam, S., Akhter, J., Pillai, K., & Morris, D. L. (2013). Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). Oncotargets and Therapy, 6, 403–409. https://doi.org/10.2147/OTT.S43072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Raeisi, F., Raeisi, E., Heidarian, E., Shahbazi-Gahroui, D., & Lemoigne, Y. (2019). Bromelain inhibitory effect on colony formation: an In vitro Study on human AGS, PC3, and MCF7 cancer cells. Journal of Medical Signals and Sensors, 9, 267–273

    Article  PubMed  PubMed Central  Google Scholar 

  39. Dhandayuthapani, S., Perez, H. D., Paroulek, A., Chinnakkannu, P., Kandalam, U., Jaffe, M., & Rathinavelu, A. (2012). Bromelain-induced apoptosis in GI-101A breast cancer cells. Journal of Medicinal Food, 15(4), 344–349. https://doi.org/10.1089/jmf.2011.0145.

    Article  CAS  PubMed  Google Scholar 

  40. Nasiri, R., Almaki, J. H., Idris, A., Nasiri, M., Irfan, M., Majid, F. A., et al. (2017). Targeted delivery of bromelain using dual mode nanoparticles: synthesis, physicochemical characterization, in vitro and in vivo evaluation. RSC Adv, 7(64), 40074–40094. https://doi.org/10.1039/C7RA06389J.

    Article  CAS  Google Scholar 

  41. Nair, H., Rao, K., Aalinkeel, R., Mahajan, S., Chawda, R., & Schwartz, S. (2004). Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clinical Diagnostic Laboratory Immunology, 11(1), 63–69. https://doi.org/10.1128/cdli.11.1.63-69.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Debnath, R., Chatterjee, N., Das, S., Mishra, S., Bose, D., Banerjee, S., et al. (2019). Bromelain with peroxidase from pineapple are more potent to target leukemia growth inhibition — a comparison with only bromelain. Toxicology in Vitro, 55, 24–32. https://doi.org/10.1016/j.tiv.2018.11.004.

    Article  CAS  PubMed  Google Scholar 

  43. Zhao, H., Zhang, Y., Sun, J., Zhan, C., & Zhao, L. (2016). Raltitrexed inhibits HepG2 cell proliferation via G0/G1 cell cycle arrest. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 23(5), 237–248. https://doi.org/10.3727/096504016X14562725373671.

    Article  Google Scholar 

  44. Borowicz, S., Van Scoyk, M., Avasarala, S., KaruppusamyRathinam, M. K., Tauler, J., Bikkavilli, R. K., & Winn, R. A. (2014). The soft agar colony formation assay. Journal of Visualized Experiments. JoVE, 92, e51998. https://doi.org/10.3791/51998.

    Article  CAS  Google Scholar 

  45. Bhui, K., Tyagi, S., Srivastava, A. K., Singh, M., Roy, P., Singh, R., & Shukla, Y. (2010). Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis. Molecular Carcinogenesis, 51(3), 231–243. https://doi.org/10.1002/mc.20769.

    Article  CAS  Google Scholar 

  46. Lee, J. H., Lee, J. T., Park, H. R., & Kim, J. B. (2019). The potential use of bromelain as a natural oral medicine having anticarcinogenic activities. Food Science & Nutrition, 7(5), 1656–1667. https://doi.org/10.1002/fsn3.999.

    Article  CAS  Google Scholar 

  47. Hanif, H. A., Murad, N. A., Wan Ngah, W. Z., & Yusof, Y. A. M. (2005). Effects of Zingiber officinale on superoxide dismutase, glutathione peroxidase, catalase, glutathione and malondialdehyde content in HepG2 cell line. Malaysian Journal of Biochemistry and Molecular Biology, 11, 36–41

    Google Scholar 

  48. Diplock, A. T., & Rice-Evans, C. A. (1993). Current status of antioxidant therapy. Free Radical Biology and Medicine, 15(1), 77–96. https://doi.org/10.1016/0891-5849(93)90127-g.

    Article  PubMed  Google Scholar 

  49. Liu, R. H., & Finley, J. (2005). Potential cell culture models for antioxidant research. Journal of Agricultural and Food Chemistry, 53, 4311–4314. https://doi.org/10.1021/jf058070i.

    Article  CAS  PubMed  Google Scholar 

  50. Kelly, L. W., & Liu, R. H. (2007). Cellular antioxidant activity (CAA) assay for assessing antioxidants, foods, and dietary supplements. Journal of Agricultural and Food Chemistry, 55(22), 8896–8907. https://doi.org/10.1021/jf0715166.

    Article  CAS  Google Scholar 

  51. El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., et al. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell, 75(4), 817–825. https://doi.org/10.1016/0092-8674(93)90500-P.

    Article  CAS  PubMed  Google Scholar 

  52. Kuo, P. L., & Lin, C. C. (2003). Green tea constituent (-)-epigallocatechin-3-gallate inhibits HepG2 cell proliferation and induces apoptosis through p53-dependent and fas-mediated pathways. Journal of Biomedical Science, 10, 219–227. https://doi.org/10.1159/000068711.

    Article  CAS  PubMed  Google Scholar 

  53. Gupta, S., Ahmad, N., Nieminen, A. L., & Mukhtar, H. (2000). Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicology and Applied Pharmacology, 164(1), 82–90. https://doi.org/10.1006/taap.1999.8885.

    Article  CAS  PubMed  Google Scholar 

  54. Choudhuri, T., Pal, S., Agwarwal, M. L., Das, T., & Sa, G. (2002). Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Letters, 512(1–3), 334–340. https://doi.org/10.1016/S0014-5793(02)02292-5.

    Article  CAS  PubMed  Google Scholar 

  55. Liontas, A., & Yeger, H. (2004). Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer Research, 24, 987–998

    CAS  PubMed  Google Scholar 

  56. Mohammad, R. Y., Somayyeh, G., Gholamreza, H., Majid, M., & Yousef, R. (2013). Diosgenin inhibits hTERT gene expression in the A549 lung cancer cell line. Asian Pacific Journal of Cancer Prevention, 14(11), 6945–6948. https://doi.org/10.7314/apjcp.2013.14.11.6945.

    Article  PubMed  Google Scholar 

  57. Raju, J., Patlolla, J. M. R., Swamy, M. V., & Rao, C. V. (2004). Diosgenin, a steroid saponin of Trigonellafoenumgraecum (fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells. Cancer Epidemiology Biomarkers and Prevention, 13(8), 1392–1398

    CAS  Google Scholar 

  58. Khalil, M. I. M., Ibrahim, M. M., El-Gaaly, G. A., & Sultan, A. S. (2015) Trigonellafoenum (fenugreek) induced apoptosis in hepatocellular carcinoma cell line, HepG2, mediated by upregulation of p53 and proliferating cell nuclear antigen. BioMed Research International, 2015, 914645.https://doi.org/10.1155/2015/914645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chi, S. W. (2014). Structural insights into the transcription-independent apoptotic pathway of p53. BMB Reports, 47(3), 167–172. https://doi.org/10.5483/BMBRep.2014.47.3.261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hientz, K., Mohr, A., Guha, B. K., & Efferth, T. (2017). The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget, 8(5), 8921–8946. https://doi.org/10.18632/oncotarget.13475.

    Article  PubMed  Google Scholar 

  61. Jin, T., George Fantus, I., & Sun, J. (2008). Wnt and beyond Wnt: multiple mechanisms control the transcriptional property of beta-catenin. Cellular Signalling, 20(10), 1697–1704. https://doi.org/10.1016/j.cellsig.2008.04.014.

    Article  CAS  PubMed  Google Scholar 

  62. Tarapore, R. S., Siddiqui, I. A., & Mukhtar, H. (2012). Modulation of Wnt/β-catenin signaling pathway by bioactive food components. Carcinogenesis, 33(3), 483–491. https://doi.org/10.1093/carcin/bgr305.

    Article  CAS  PubMed  Google Scholar 

  63. Wang, D., Wise, M. L., Li, F., & Dey, M. (2012). Phytochemicals attenuating aberrant activation of β-catenin in cancer cells. PLoS ONE, 7(12), e50508. https://doi.org/10.1371/journal.pone.0050508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Cheng, X., Xu, X., Chen, D., Zhao, F., & Wang, W. (2019). Therapeutic potential of targeting the Wnt/beta-catenin signaling pathway in colorectal cancer. Biomedicine and Pharmacotherapy, 110(Feb), 473–481. https://doi.org/10.1016/j.biopha.2018.11.082.

    Article  CAS  PubMed  Google Scholar 

  65. Willenbacher, E., Khan, S. Z., Mujica, S. C. A., Trapani, D., Hussain, S., & Wolf, D. (2019). Curcumin: new insights into an ancient ingredient against cancer. International Journal of Molecular Sciences, 20(8), 1–13. https://doi.org/10.3390/ijms20081808.

    Article  CAS  Google Scholar 

  66. Amado, N. G., Predes, D., Moreno, M. M., Carvalho, I. O., Mendes, F. A., & Abreu, J. G. (2014). Flavonoids and Wnt/beta-catenin signaling: potential role in colorectal cancer therapies. International Journal of Molecular Sciences, 15(7), 12094–12106. https://doi.org/10.3390/ijms150712094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kahn, M. (2014). Can we safely target the WNT pathway? Nature Reviews Drug Discovery, 13(7), 513–532. https://doi.org/10.1038/nrd4233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Farahmand, L., Darvishi, B., Majidzadeh, A. K., & Madjid Ansari, A. (2017). Naturally occurring compounds acting as potent anti-metastatic agents and their suppressing effects on Hedgehog and WNT/beta-catenin signalling pathways. Cell Proliferation, 50(1), e12299. https://doi.org/10.1111/cpr.12299.

    Article  CAS  Google Scholar 

  69. Park, S., & Choi, J. (2010). Inhibition of beta-catenin/Tcf signaling by flavonoids. Journal of Cellular Biochemistry, 110(6), 1376–1385. https://doi.org/10.1002/jcb.22654.

    Article  CAS  PubMed  Google Scholar 

  70. Fuentes, R. G., Arai, M. A., & Ishibashi, M. (2015). Natural compounds with Wnt signal modulating activity. Natural Products Reports, 32, 1622–1628. https://doi.org/10.1039/C5NP00074B.

    Article  CAS  Google Scholar 

Download references

Acknowledgement

The authors are thankful to the Department of Chemical Engineering, JNTUA College of Engineering, Ananthapuram, India for providing space in completing the study successfully.

Author information

Authors and Affiliations

  1. Department of Biotechnology, JNTUA College of Engineering, Ananthapuram, 515002, Andhra Pradesh, India

    Sushma S. Murthy

  2. Department of Chemical Engineering, JNTUA College of Engineering, Ananthapuram, 515002, Andhra Pradesh, India

    T. Bala Narsaiah

Authors
  1. Sushma S. Murthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Bala Narsaiah
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Sushma S Murthy and T. Bala Narasaiah conceived and designed the experiment. Sushma S Murthy performed the experiment related to the anti-cancer property of bromelain in HepG2 cell lines, and studied the effect of bromelain on p53 and β-catenin protein expression. Validation of the experiments and manuscript writing were done by T Bala Narsaiah and Sushma S Murthy. Sushma S Murthy revised and reviewed the manuscript. Both authors read and approved the present manuscript.

Corresponding author

Correspondence to Sushma S. Murthy.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

The present article does not involve any human and animal participation in experiments performed by authors. Therefore, no formal consent is needed.

Consent to Participate

Not applicable.

Consent to Publish

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murthy, S.S., Narsaiah, T.B. Cytotoxic Effect of Bromelain on HepG2 Hepatocellular Carcinoma Cell Line. Appl Biochem Biotechnol 193, 1873–1897 (2021). https://doi.org/10.1007/s12010-021-03505-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-021-03505-z

Keywords

Search

Navigation