Ferdowsi University of Mashhad

Document Type : Research Articles


1 Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

2 Department of Biotechnology and Plat Breeding, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran

3 Blood Transfusion Research Center High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

4 Department of Clinical Biochemistry and Genetics, Mazandaran University of Medical Science, Iran


Royal jelly (RJ) from queen honeybee larva as a traditional medicine agent has a variety of pharmacological benefits. In the present study, the effect of Royal jelly was investigated on the urinary bladder cancer cell line (HTB-9 5637). To determine the cell viability in different concentrations of Royal jelly, MTT assay was performed. An in vitro wound healing assay was applied to investigate the effect of RJ on cell migration. The activity and gene expression level of matrix metalloproteinase 2 and 9 was assessed by zymography and Real time PCR respectively. R.J.S at the concentration of 0.7 mg/ml had a significant effect on reducing the proliferation rate of 5637 cells after 72h (p < 0.009). R.J.S significantly decreased cell migration and induced a significant decrease in the transcriptional level of MMP9 after 72h (0.5x; P < 0.049). However R.J.S did not impose any effect on the expression level and activity of matrix metalloproteinase 2. These results indicate the potential of RJ as a promised natural anti-proliferative and anti-metastatic drug in combination with advanced therapy methods for cancer treatment. Royal jelly has the potential to be more focused as an anti-metastatic drug to control tumor growth and can be considered as a more effective alternative to the current chemotherapy drugs.


Aparna J. and Brundha M. (2020) Matrix Metalloproteinases (MMPS) and its Role in Cancers-A Review. Indian Journal of Forensic Medicine & Toxicology 14.
Bergers G., Brekken R., McMahon G., Vu T. H., Itoh T., Tamaki K., and et al. (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature cell biology 2:737-744.
Cieckiewicz E., Angenot L., Gras T., Kiss R. and Frédérich M. (2012) Potential anticancer activity of young< i> Carpinus betulus leaves. Phytomedicine 19:278-283.
 Didar G., Delpazir F., Kaviani M., Azarpira N., Sepehrara L., Ebadi P. and Koohpeyma F. (2019) Influence of mesenchymal stem cells and royal jelly on kidney damage triggered by ischemia-reperfusion injury: comparison with ischemic preconditioning in an animal model. Comparative Clinical Pathology 28:311-320.
 Erem C., Deger O., Ovali E. and Barlak Y. (2006) The effects of royal jelly on autoimmunity in Graves' disease. Endocrine 30:175-183.
Gasic S., Vucevic D., Vasilijic S., Antunovic M., Chinou I. and Colic M. (2007) Evaluation of the immunomodulatory activities of royal jelly components in vitro. Immunopharmacology and immunotoxicology 29:521-536.
Gialeli C., Theocharis A. D. and Karamanos N. K. (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FeBS Journal 278:16-27.
Huerta-Yepez S., Vega M., Garban H. and Bonavida B. (2006) Involvement of the TNF-α autocrine–paracrine loop, via NF-κB and YY1, in the regulation of tumor cell resistance to Fas-induced apoptosis. Clinical immunology 120:297-309.
Izuta H., Chikaraishi Y., Shimazawa M., Mishima S. and Hara H. (2009) 10-Hydroxy-2-decenoic acid, a major fatty acid from royal jelly, inhibits VEGF-induced angiogenesis in human umbilical vein endothelial cells. Evidence-based complementary and alternative medicine 6:489-494.
Karadeniz A., Simsek N., Karakus E., Yildirim S., Kara A., Can I., and et al. (2011) Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats treated with cisplatin. Oxidative medicine and cellular longevity 2011.
Kessenbrock K., Plaks V. and Werb Z. (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52-67.
Kim J., Kim Y., Yun H., Park H., Kim S. Y., Lee K.-G., Han S.-M. and Cho Y. (2010) Royal jelly enhances migration of human dermal fibroblasts and alters the levels of cholesterol and sphinganine in an in vitro wound healing model. Nutrition research and practice 4:362-368.
Kohno K., Okamoto I., Sano O., Arai N., Iwaki K., Ikeda M. and Kurimoto M. (2004) Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Bioscience, biotechnology, and biochemistry 68:138-145.
Lee S.-J., Park S.-S., Lee U.-S., Kim W.-J. and Moon S.-K. (2008) Signaling pathway for TNF-α-induced MMP-9
expression: mediation through p38 MAP kinase, and inhibition by anti-cancer molecule magnolol in human urinary bladder cancer 5637 cells. International immunopharmacology 8:1821-1826.
Miyata Y. and Sakai H. (2018) Anti-cancer and protective effects of royal jelly for therapy-induced toxicities in malignancies. International journal of molecular sciences 19:3270.
Okamoto I., Taniguchi Y., Kunikata T., Kohno K., Iwaki K., Ikeda M. and Kurimoto M. (2003) Major royal jelly protein 3 modulates immune responses in vitro and in vivo. Life sciences 73:2029-2045.
Ramanathan A. N. K. G., Nair A. J. and Sugunan V. S. (2018) A review on Royal Jelly proteins and peptides. Journal of Functional Foods 44:255-264.
Reis S. T., Leite K. R. M., Piovesan L. F., Pontes-Junior J., Viana N. I., Abe D. K., and et al. (2012) Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer. BMC urology 12:18.
Ricci S., Bruzzese D. and Di Carlo A. (2015) Evaluation of MMP‑2, MMP‑9, TIMP‑1, TIMP‑2, NGAL and MMP‑9/NGAL complex in urine and sera from patients with bladder cancer. Oncology letters 10:2527-2532.
Saginala K., Barsouk A., Aluru J. S., Rawla P., Padala S. A. and Barsouk A. (2020) Epidemiology of bladder cancer. Medical Sciences 8:15.
Saini S., Arora S., Majid S., Shahryari V., Chen Y., Deng G., and et al. (2011) Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev Res (Phila) 4:1698-1709.
Salazar-Olivo L. and Paz-Gonzalez V. (2005) Screening of biological activities present in honeybee (< i> Apis mellifera) royal jelly. Toxicology in vitro 19:645-651.
Shi Y. Y., Huang Z. Y., Zeng Z. J., Wang Z. L., Wu X. B. and Yan W. Y. (2011) Diet and cell size both affect queen-worker differentiation through DNA methylation in honey bees (Apis mellifera, Apidae). PloS one 6:e18808.
Sugiyama T., Takahashi K. and Mori H. (2012) Royal jelly acid, 10-hydroxy-trans-2-decenoic acid, as a modulator of the innate immune responses. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 12:368-376.
Viuda‐Martos M., Ruiz‐Navajas Y., Fernández‐López J. and Pérez‐Álvarez J. (2008) Functional properties of honey, propolis, and royal jelly. Journal of food science 73:R117-R124.
Volpe A., Racioppi M., D'Agostino D., D'Addessi A., Marangi F., Totaro A., and et al. (2013) Advanced bladder cancer: new agents and new approaches. A review. In Urologic Oncology: Seminars and Original Investigations. Vol. 31. Elsevier. 9-16.
Zhang L., Fang Y., Li R., Feng M., Han B., Zhou T. and Li J. (2012) Towards posttranslational modification proteome of royal jelly. Journal of proteomics 75:5327-5341.
Zhang S., Shao Q., Geng H. and Su S. (2017) The effect of royal jelly on the growth of breast cancer in mice. Oncology letters 14:7615-7621.
Zidi I., Mestiri S., Bartegi A. and Amor N. B. (2010) TNF-α and its inhibitors in cancer. Medical Oncology 27:185-198.