Volume: 44 Issue: 1
Year: 2024, Page: 107-113, Doi: https://doi.org/10.51248/.v44i1.4152
Received: Dec. 5, 2023 Accepted: Feb. 1, 2024 Published: May 1, 2024
Introduction and Aim: Breast cancer ranks among the leading causes of death in women worldwide. Ginger has shown potential efficacy against certain cancer types, surpassing conventional therapies such as chemotherapy and radiation. However, its molecular mechanisms remain less understood.
Materials and Methods: In this study, MCF-7 cancer cells were cultured and treated with various concentrations of aqueous ginger extract (20, 30, 45, 65 μg/mL) for 12, 48, and 72 hours. The effects were assessed through gene expression analysis and cell vitality assays (MTT).
Results: The cell vitality test revealed a direct correlation between cytotoxicity and extract concentration. Concentrations exceeding 30 μg/mL exhibited significant cell death (IC50 of 104.03 μg/mL). Gene expression analysis demonstrated an increase in Patched-1 and a decrease in Gli1 expression with rising extract concentrations. The maximum Patched-1 expression occurred at 65 μg/mL after 72 hours. Patched-1 (oncogene) and Gli1 (tumor suppressor) are pivotal genes in the hedgehog (Hh) signalling pathway associated with breast cancer.
Conclusion: It appears that ginger compounds play a substantial role in regulating cancer progression by influencing key components of the hedgehog signalling pathway.
Keywords: Ginger extract; breast cancer; gene expression analysis; Patched-1; Gli1.
1. Vo, A.T., Millis, R. M. Epigenetics and breast cancers. Obstetrics and Gynecology International. 2012; 602720:1-10.
2. Hirsch, B. R., Lyman, G. H. Breast cancer screening with mammography. Current Oncology Reports. 2011; 13(1):63-70.
3. Mousavi, S. M., Montazeri, A., Mohagheghi, M. A., Jarrahi, A. M., Harirchi, I., Najafi, M., et al., Breast cancer in Iran: An epidemiological review. The Breast Journal. 2007;13:383-391.
4. Turaga, K., Acs, G., Laronga, C. Gene expression profiling in breast cancer. Cancer Control. 2010;17:177-182.
5. Sultan Aslantürk, Ö., Aşkın Çelik, T. Antioxidant activity and anticancer effect of Vitex agnus-castus L.(Verbenaceae) seed extracts on MCF–7 breast cancer cells. Caryologia: International Journal of Cytology, Cyto-systematics, and Cytogenetics. 2013;66(3):257-267.
6. Sakarkar, D. M., Deshmukh, V. N. Ethnopharmacological review of traditional medicinal plants for anticancer activity. International Journal of PharmTech Research.2011;3(1):298-308.
7. Malhotra, S., Singh, A. P. Medicinal properties of ginger (Zingiber officinale Rosc.). Natural Product Radiance. 2003; 2(6):296-301.
8. Elkady, A. I., Abuzinadah, O. A., Baeshen, N. A., Rahmy, T. R. Differential control of growth, apoptotic activity, and gene expression in human breast cancer cells by extracts derived from medicinal herbs Zingiber officinale. BioMed Research International. 2012; 614356.
9. Wang, H., Ng, T. B. An antifungal protein from ginger rhizomes. Biochem Biophys Res Commun. 2005;336(1):100-104.
10. Jeyakumar, S. M., Nalini, N., Menon, V. P. Antioxidant activity of ginger (Zingiber officinale Rosc) in rats fed a high fat diet. Medical Science Research. 1999; 27:341-344.
11. Shukla, Y., Singh, M. Cancer preventive properties of ginger: a brief review. Food Chem Toxicol. 2007;45:683-690.
12. Gupta, Y. K., Sharma, M. Reversal of pyrogallol-induced delay in gastric emptying in rats by ginger (Zingiber officinale). Methods and Findings in Experimental and Clinical Pharmacology. 2001;23:501-503.
13. Bhattarai, S., Tran, V. H., Duke C. C. The stability of gingerol and shogaol in aqueous solutions. Journal of Pharmaceutical Sciences. 2001;90:1658-1664.
14. Park, K. K., Chun, K. S., Lee, J. M., Lee, S. S., Surh, Y. J. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Letters. 1998;129;139-144.
15. Bode, A. M, Ma, W. Y., Surh, Y. J., Dong, Z. Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol. Cancer Research. 2001;61:850-853.
16. Park, Y. J., Wen, J., Bang, S., Park, S. W., Song, S. Y. [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. Yonsei Medical Journal. 2006;47:688-697.
17. Habib, S. H., Makpol, S., Hamid, N. A., Das, S., Ngah, W. Z., Yusof, Y. A. Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics. 2008;63:807-813.
18. Jeong, C. H., Bode, A. M., Pugliese, A., Cho, Y. Y., Kim, H. G., Shim, J. H., et al., [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Research. 2009;69:5584-5591.
19. Lee, H. S., Seo, E. Y., Kang, N. E., Kim, W. K. [6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells. The Journal of Nutritional Biochemistry. 2008;19:313-319.
20. Al-Ziyadi, R. K. M., Hayati, N., Rezaei, M. R., Es-haghi, A. Preparation and characterization of chitosan-coated nanostructured lipid carriers (CS-NLC) containing (6)-gingerol and investigating their toxicity against MCF-7 breast cancer cell line. BioNanoScience. 2024; 14:153-163.
21. Romijn, J. C., Verkoelen, C. F., Schroeder, F. H. Application of the MTT assay to human prostate cancer cell lines in vitro: Establishment of test conditions and assessment of hormone‐stimulated growth and drug‐induced cytostatic and cytotoxic effects. The Prostate. 1988;12: 99-110.
22. Davoren, P. A., McNeill, R. E., Lowery, A. J., Kerin, M. J., Miller, N. Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer. BMC Molecular Biology. 2008; PMC2533012: 9-76.
23. Schmittgen, T. D., Livak, K. Analyzing real-time PCR data by the comparative CT method. Nature Protocols. 2011;3:1101-1108.
24. Kubo, M., Nakamura, M., Tasaki, A., Yamanaka, N., Nakashima, H., Nomura, M., et al., Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Research. 2004; 64:6071-6074.
25. Mukherjee, S., Frolova, N., Sadlonova, A., Novak, Z., Steg, A., Page, G., et al., Hedgehog signaling and response to cyclopamine differs in epithelial and stromal cells in benign breast and breast cancer. Cancer Biology and Therapy. 2006; 5:674-683.
Seyedeh Mahsa Torabi, Mahdi Rahaie, Asa Ebrahimi. The effect of ginger extract on expression of Gli1 and Patched-1 genes involved in breast cancer signaling pathway under in vitro condition. Biomedicine: 2024; 44(1): 107-113