Transcriptional Expression of Bcl-2, Her2, VEGF, and hTERT in Caki-1 Human Renal Cancer Cells Modulated by Cornus mas Extract

IRCMJ logo
PDF
HTML

Keywords

Bcl-2
Cornus mas extract
Her2
, hTERT
Renal cancer
VEGF

How to Cite

JiJ., HouS., GaoY., FengX., & LiS. (2020). Transcriptional Expression of Bcl-2, Her2, VEGF, and hTERT in Caki-1 Human Renal Cancer Cells Modulated by Cornus mas Extract. Iranian Red Crescent Medical Journal, 22(11). https://doi.org/10.32592/ircmj.2020.22.11.198

Abstract

Background: Herbal medicines, particularly those rich in polyphenolic compounds, have been proposed to be chemotherapeutic factors, which can modulate several pathways associated with cancer. To gain mechanistic insights into the anti-proliferative impacts of Cornus mas extract (CME), this study investigated the expression changes of several prominent genes, which involved in malignancy with therapeutic potential.

Objectives: The aim of the study was to determine the anticancer potential of CME on the main regulatory genes in renal carcinogenesis.

Methods: To perform the research, Caki-1 cancer cells were incubated for 72 h with 250 µg/ml of CME upon the cells with ribonucleic acids (RNAs) extracted for identified alterations of human telomerase reverse transcriptase (hTERT), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2), and B-cell lymphoma-2 (Bcl-2) gene expressions by a quantitative reverse transcription-polymerase chain reaction. The changes in protein expression were analyzed by the western blot method. Cell apoptosis was detected using the flow cytometry technique. 

Results: Cornus mas extract caused down-regulated Bcl-2 as an anti-apoptotic 4.34-fold gene expression. Moreover, Her2 oncogene messenger RNA expression was inhibited by 250 µg/ml concentration of ~10-fold CME. The antitumor activity of CME was pronounced in its potent anti-angiogenic potential, as CME resulted in a striking decrease in ~125-fold expression of VEGF compared to the untreated control. In contrast, CME led to ~2.6-fold up-regulation of hTERT in Caki-1 cancer cells.

Conclusion: Overall, various molecular pathways were formed to interplay with Caki-1 cells, which depended on the active phenolic compound of CME. It is recommended to perform further studies to investigate the effect of unique polyphenols of the total extract of CME to establish an effective strategy for renal cancer treatment.

https://doi.org/10.32592/ircmj.2020.22.11.198
PDF
HTML

References

  1. Ashtiani M, Nabatchian F, Galavi HR, Saravani R, Farajian-Mashhadi F, Salimi S. Effect of Achillea wilhelmsii extract on expression of the human telomerase reverse transcriptase mRNA in the PC3 prostate cancer cell line. Biomed Rep. 2017;7(3):251-6. doi: 10.3892/br.2017.956. [PubMed: 28811896].
  2. Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63-89. doi: 10.14740/wjon1191. [PubMed: 31068988].
  3. Grönberg H. Prostate cancer epidemiology. Lancet. 2003;361(9360):859-64. doi: 10.1016/S0140-6736(03)12713-4
  4. Lee DH, Szczepanski MJ, Lee YJ. Magnolol induces apoptosis via inhibiting the EGFR/PI3K/Akt signaling pathway in human prostate cancer cells. J Cell Biochem. 2009;106(6):1113-22. doi: 10.1002/jcb.22098. [PubMed: 19229860].
  5. Zhang Y, Liang Y, He C. Anticancer activities and mechanisms of heat-clearing and detoxicating traditional Chinese herbal medicine. Chin Med. 2017;12(1):20. doi: 10.1186/s13020-017-0140-2. [PubMed: 28702078].
  6. Cho HS, Park JH, Kim YJ. Epigenomics: novel aspect of genomic regulation. J Biochem Mol Biol. 2007;40(2):151-5. doi: 10.5483/bmbrep.2007.40.2.151. [PubMed: 17394763].
  7. Haddad AQ, Venkateswaran V, Viswanathan L, Teahan SJ, Fleshner NE, Klotz LH. Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer Prostatic Dis. 2006;9(1):68-76. doi: 10.1038/sj.pcan.4500845. [PubMed: 16314891].
  8. Kazimierski M, Regula J, Molska M. Cornelian cherry (Cornus mas L.) - characteristics, nutritional and pro-health properties. Acta Sci Pol Technol Aliment. 2019;18(1):5-12. doi: 10.17306/J.AFS.0628. [PubMed: 30927747].
  9. Krosniak M, Gastol M, Szalkowski M, Zagrodzki P, Derwisz M. Cornelian cherry (cornus MAS L.) juices as a source of minerals in human diet. J Toxicol Environ Health A. 2010;73(17-18):1155-8. doi: 10.1080/15287394.2010.491408. [PubMed: 20706938].
  10. Pantelidis GE, Vasilakakis M, Manganaris GA, Diamantidis GR. Antioxidant capacity, phenol, anthocyanin and ascorbic acid contents in raspberries, blackberries, red currants, gooseberries and Cornelian cherries. Food Chem. 2007;102(3):777-83. doi:10.1016/j.foodchem.2006.06.021.
  11. Pyrkosz-Biardzka K, Kucharska AZ, Sokół-Łętowska A, Strugała P, Gabrielska J. A comprehensive study on antioxidant properties of crude extracts from fruits of Berberis vulgaris L., Cornus mas L. and Mahonia aquifolium Nutt. Pol J Food Nut Sci. 2014;64(2):91-9.
    doi: 10.2478/v10222-012-0097-x.
  12. Wang L-S, Stoner GD. Anthocyanins and their role in cancer prevention. Cancer Lett. 2008;269(2):281-90. doi: 10.1016/j.canlet.2008.05.020. [PubMed: 18571839].
  13. Nabavi SM, Šamec D, Tomczyk M, Milella L, Russo D, Habtemariam S, et al. Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering. Biotechnol Adv. 2020;38:107316. doi: 10.1016/j.biotechadv.2018.11.005. [PubMed: 30458225].
  14. Bradner JE, Hnisz D, Young RA. Transcriptional Addiction in Cancer. Cell. 2017;168(4):629-43. doi: 10.1016/j.cell.2016.12.013. [PubMed: 28187285].
  15. Herrington CS, Poulsom R, Coates PJ. Recent advances in pathology: the 2020 annual review issue of the journal of pathology. J Pathol. 2020;250(5):475-9. doi: 10.1002/path.5425. [PubMed: 32346919].
  16. Adamenko K, Kawa-Rygielska J, Kucharska AZ, Piorecki N. Characteristics of biologically active compounds in cornelian cherry meads. Molecules. 2018;23(8)2024. doi: 10.3390/molecules23082024. [PubMed: 3011900].
  17. Gąstoł M, Krośniak M, Derwisz M, Dobrowolska-Iwanek J. Cornelian cherry (Cornus mas L.) juice as a potential source of biological compounds. J Med Food. 2013;16(8):728-32. doi: 10.1089/jmf.2012.0248. [PubMed: 23905648].
  18. Forman V, Haladová M, Grančai D, Ficková M. Antiproliferative activities of water infusions from leaves of five cornus l. species. Molecules. 2015;20(12):22546-52. doi: 10.3390/molecules201219786. [PubMed: 26694338].
  19. Cao H, Feng Y, Chen L, Yu C. Lobaplatin inhibits prostate cancer proliferation and migration through regulation of bcl2 and bax. Dose Response. 2019;17(2):1559325819850981. doi: 10.1177/1559325819850981. [PubMed: 31217754].
  20. Gandour-Edwards R, Mack PC, deVere-White RW, Gumerlock PH. Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 2004;7(4):321-6. doi: 10.1038/sj.pcan.4500749. [PubMed: 15314639].
  21. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997;275(5303):1129-32. doi: 10.1126/science.275.5303.1129. [PubMed: 9027314].
  22. Lee DH, Szczepanski M, Lee YJ. Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochem Pharmacol. 2008;75(12):2345-55. doi: 10.1016/j.bcp.2008.03.013. [PubMed: 18455702].
  23. Andersson J, Rosestedt M, Asplund V, Yavari N, Orlova A. In vitro modeling of HER2-targeting therapy in disseminated prostate cancer. Int J Oncol. 2014;45(5):2153-8. doi: 10.3892/ijo.2014.2628. [PubMed: 25176024].
  24. Banerjee S, Singh SK, Chowdhury I, Lillard Jr JW, Singh R. Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer. Front Biosci (Elite ED). 2017;9:235-45. doi: 10.2741/e798. [PubMed: 8199187].
  25. Ghanbari P, Mohseni M, Tabasinezhad M, Yousefi B, Saei AA, Sharifi S, et al. Inhibition of survivin restores the sensitivity of breast cancer cells to docetaxel and vinblastine. Appl Biochem Biotechnol. 2014;174(2):667-81. doi: 10.1007/s12010-014-1125-6. [PubMed: 25086926].
  26. Yousefi B, Samadi N, Ahmadi Y. Akt and p53R2, partners that dictate the progression and invasiveness of cancer. DNA Repair (Amst). 2014;22:24-9. doi: 10.1016/j.dnarep.2014.07.001. [PubMed: 25086499].
  27. Liu N, Ding D, Hao W, Yang F, Wu X, Wang M, et al. hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor. Nucleic Acids Res. 2016;44(18):8693-703. doi: 10.1093/nar/gkw549. [PubMed: 27325744].
  28. Melegh Z, Oltean S. Targeting angiogenesis in prostate cancer. Int J Mol Sci. 2019;20(11):2676. doi: 10.3390/ijms20112676. [PubMed: 31151317].
  29. Bender RJ, Mac Gabhann F. Dysregulation of the vascular endothelial growth factor and semaphorin ligand-receptor families in prostate cancer metastasis. BMC Syst Biol. 2015