Anti-tumor activity of ginger extracts in MCF-7 breast cancer cells

Document Type : Original research


1 Department of Biology, University of Zabol, Zabol, Iran

2 Department of Cell & Molecular Sciences, Kharazmi Universty, Tehran, Iran

3 Department of Animal Science, University of Zabol, Zabol, Iran

4 Department of Molecular Biology, Tofigh Daru Co., Tehran, Iran

5 Department of Chemistry, University of Zabol, Zabol, Iran

6 Department of Biotechnology, Alzahra University, Tehran, Iran

7 Department of Science Payame Noor University, Tehran, Iran

8 Departments of Ophthalmology & Visual Sciences, Cell & Regenerative Biology, & Biomedical Engineering, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA



Breast cancer is the most common form of cancer in women, and the second leading causes of death in the world. Clinical efficacy of chemotherapy is limited due to side effects, toxicity, and drug resistance. Plant-derived anticancer drugs are new promising compounds, which show their anticancer activity through activation of apoptotic pathways. Ginger is a flowering plant with active phenolic compounds that exhibit anticancer activity. Here we studied the effect of ginger acetone, ethanol and methanol extracts on the MCF-7 breast cancer using MTT assay, Real time-PCR and normal inverted microscope. MCF-7 breast cancer cells were incubated with 2.5, 5 and 10 μg/mL of ginger extracts for 48 h. The survival of incubated MCF-7 cells with ginger extracts, indicated significantly decreased. The most dramatic effect was noted in cells incubated with acetone extracts, 10 μg/mL for 48 h compared to the control. Moreover, by increasing the concentration of ethanolic ginger extract, the cell vitality decreased significantly. Real-time PCR results showed that the expression of Bcl-2 was significantly decreased in cells incubated with ginger extracts. Decrease of Bcl-2 expression can cause increase apoptotic pathways and reduction of cancer cell survival. Thus, extract of ginger destroys breast cancer cells and other cancers cells and improves health.


Main Subjects

Abdullah, S., Abidin, S. A. Z., Murad, N. A., Makpol, S., Ngah, W. Z. W., & Yusof, Y. A. M. (2010). Ginger extract (Zingiber officinale) triggers apoptosis and G0/G1 cells arrest in HCT 116 and HT 29 colon cancer cell lines. African Journal of Biochemistry Research, 4, 134-142.
Abedini, M. R., Erfanian, N., Nazem, H., Jamali, S., & Hoshyar, R. (2016). Anti-proliferative and apoptotic effects of Ziziphus jujube on cervical and breast cancer cells. Avicenna journal of phytomedicine, 6, 142.
Allred, D. C. (2010). Ductal carcinoma in situ: terminology, classification, and natural history. Journal of the National Cancer Institute Monographs, 2010, 134-138.
Anderson, K. N., Schwab, R. B., & Martinez, M. E. (2014). Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast cancer research and treatment, 144, 1-10.
Ayob, A. Z., & Ramasamy T. S. (2018). Cancer stem cells as key drivers of tumour progression. Journal of Biomedical Science, 25, 1-18.
Baer, R. (1994). Bcl-2 breathes life into embryogenesis. The American journal of pathology 145, 7.
Banerjee, S., Mullick, H., Banerjee, J., & Ghosh, A. (2011). Zingiber officinale:‘a natural gold’. International Journal of Pharma and Bio Sciences, 2, 283-294.
Behbahani, M. (2014). Evaluation of in vitro anticancer activity of Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. PLoS One, 9(12), e116049.  
Bong, I., Lim, P., Balraj P., Sim Ui Hang, E., & Zakaria, Z. (2006). Quantitative analysis of the expression of p53 gene in colorectal carcinoma by using real-time PCR. Tropical Biomedicine, 23, 53–59.
Chabner, B. A., & Friedman, M. A. (1992). Progress against rare and not-so-rare cancers. The New England Journal of Medicine, 326(8), 563-5.
Chatupheeraphat, C., Roytrakul, S., Phaonakrop, N., Deesrisak, K., Krobthong, S., Anurathapan, U., & Tanyong, D. (2021). A novel peptide derived from ginger induces apoptosis through the modulation of p53, BAX, and BCL2 expression in leukemic cell lines. Planta Medica, 87(7), 560-569.
DeSantis, C. E., Lin, C. C., Mariotto, A. B., Siegel, R. L., Stein, K. D., Kramer, J. L., Alteri, R., Robbins, A. S., & Jemal, A. (2014). Cancer treatment and survivorship statistics, 2014. CA: A Cancer Journal for Clinicians, 64, 252-271.
Dasari, S., Njiki, S., Mbemi, A., Yedjou, C. G., & Tchounwou, P. B. (2022). Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy. International Journal of Molecular Sciences, 23, 1532.
El Kichaoui, A. Y., Ayesh, B. M., & Aliwaini, S. H. (2016). The use of some plant extracts as an alternative approaches for treatment of certain malignant cell lines. Journal of Medicinal Plants Studies, 4, 174-188.
Hashem, S., Ali, T. A., Akhtar, S., Nisar, S., Sageena, G., Ali, S., Al-Mannai, S., Therachiyil, L., Mir, R., Elfaki, I., Mir, M. M., Jamal, F., Masoodi, T., Uddin, S., Singh, M., Haris, M., Macha, M., & Bhat, A. A. (2022). Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents. Biomedicine & Pharmacotherapy, 150, 113054.
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990). Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 348, 334-336.
Hu, R., Zhou, P., Peng, Y. B., Xu, X., Ma, J., Liu, Q., Zhang, L., Wen, X. D., Qi, L. W., Gao, N., &  Li, P. (2012) 6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress. PLoS One, 7, e39664.
Hwang, K. T., Woo, J. W., Shin, H. C., Kim, H. S., Ahn, S. K., Moon, H. G., Han, W., Park, I., & Noh, D. Y. (2012). Prognostic influence of BCL2 expression in breast cancer. International Journal of Cancer, 131, e1109-19.
Kim, S. O., Chun, K. -S., Kundu, J. K., & Surh, Y. -J. (2004). Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-κB and p38 MAPK in mouse skin. BioFactors, 21, 27-31.
Kizhakkayil, J., & Sasikumar, B. (2012). Characterization of ginger (Zingiber officinale Rosc.) germplasm based on volatile and non-volatile components. African Journal of Biotechnology, 11, 777-786.
Kotowski, U., Kadletz, L., Schneider, S., Foki, E., Schmid, R., Seemann, R., Thurnher, D., & Heiduschka, G. (2019). 6-shogaol induces apoptosis and enhances radiosensitivity in head and neck squamous cell carcinoma cell lines. Phytotherapy Research, 32, 340–347.
Larsen, M. J., Thomassen, M., Gerdes, A. M., & Kruse, T. A. (2014). Hereditary breast cancer: clinical, pathological and molecular characteristics. Breast Cancer: Basic & Clinical Research, 8, BCBCR-S18715.
Lechner, J. F., & Stoner, G. D. (2019). Gingers, and their purified components as cancer chemopreventative agents. Molecules24, 2859.
Łukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., & Stanisławek, A. (2021). Breast cancer-epidemiology, risk factors, classification, prognostic markers, and current treatment strategies: An updated review. Cancers (Basel), 13(17), 4287.
Mansingh, D. P., Sunanda, O. J., Sali,V. K., & Vasanthi, H. R. (2018). [6]-Gingerol-induced cell cycle arrest, reactive oxygen species generation, and disruption of mitochondrial membrane potential are associated with apoptosis in human gastric cancer (AGS) cells. Journal of Biochemical and Molecular Toxicology, 32(10), e22206.
Marzo, I., & Naval, J. (2008). Bcl-2 family members as molecular targets in cancer therapy. Biochemical pharmacology, 76, 939-946.
Merino, D., Lok, S. W., Visvader, J. E., & Lindeman, G. J. (2016). Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer. Oncogene, 35(15), 1877-87.
Nigam, N., Bhui, K., Prasad, S., George, J., & Shukla, Y. (2009). [6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells. Chemico-biological Interactions 181, 77-84.
Pal, S. K., & Shukla, Y. (2003). Herbal medicine:  current status and the future. Asian Pacific Journal of Cancer Prevention, 4, 281-288.
Pashaei-Asl, R., Pashaei-Asl, F., Gharabaghi, P. M., Khodadadi, K., Ebrahimi, M., Ebrahimie, E., & Pashaiasl, M. (2017). The inhibitory effect of ginger extract on Ovarian cancer cell line; Application of systems biology. Advanced pharmaceutical bulletin, 7, 24-249.
Pfeffer, C. M., & Singh, A. T. (2018). Apoptosis: A target for anticancer therapy. International Journal of Molecular Sciences, 19, 448.
Rajalingam, K., Schreck, R., Rapp, U. R., & Albert, Š. (2007). Ras oncogenes and their downstream targets. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1773, 1177-1195.
Rajasekharan, S., & Raman, T. (2013). Ras and ras mutations in cancer. Open Life Sciences, 8, 609-6.
Redondo, M. (2013). Bcl-2, an antiapoptotic gene indicator of good prognosis in breast cancer: The paradox. Journal of Carcinogenesis & Mutagenesis, 4, 135-139.
Saeedifar, A. M., Mosayebi, G., Ghazavi , A., &  Ganji, A. (2020). Synergistic evaluation of ginger and licorice extracts in a mouse model of colorectal cancer. Nutrition & Cancer, 73(2), 1-11.
Sheikhbahaei, F., Khazaei, M., & Nematollahi-Mahani, S. N. (2018). Teucrium polium extract enhances the anti-angiogenesis effect of tranilast on human umbilical vein endothelial cells. Advanced Pharmaceutical Bulletin, 8(1), 131-139.
Shukla, Y., & Singh, M. (2007). Cancer preventive properties of ginger: A brief review. Food and chemical toxicology, 45, 683-690.
Siegel, R. L., Miller, K. D., & Jemal, A. (2016). Cancer statistics, 2016. CA: A cancer Journal for Clinicians, 66, 7-30.
Stankovic, M. S., Curcic, M. G., Zizic, J. B., Topuzovic, M. D., Solujic, S. R., Markovic, S. D. (2011). Teucrium plant species as natural sources of novel anticancer compounds:  Antiproliferative, proapoptotic and antioxidant properties. International Journal of Molecular Sciences, 12(7), 4190-205.
Talib , W. H.,  Awajan, D. ,  Hamed, R. A.,  Azzam, A. O.,  Mahmod, A. I., &  Al-Yasari, I. H. (2022). Combination anticancer therapies using selected phytochemicals. Molecules, 27, 5452.
Wang, C. C., Chen, L. -G., Lee, L. -T., & Yang, L. -L. (2003). Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells. In vivo (Athens, Greece),  17(6), 641-645.
Zadorozhna, M., & Mangieri, D. (2021). Mechanisms of chemopreventive and therapeutic proprieties of ginger extracts in cancer. International Journal of Molecular Science, 22(12), 6599.
Zeydi, A. E. (2016). Teucrium polium plant extract as a novel anticancer agent in the near future: Is it possible?. Indian Journal of Cancer, 53(1), 66.
Zick, S. M., Ruffin, M. T., Lee, J., Normolle, D. P., Siden, R., Alrawi, S., & Brenner, D. E. (2009). Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting. Support Care Cancer, 17, 563–572.
Zick, S. M., Turgeon, D. K., Ren, J., Ruffin, M. T., Wright, B. D., Sen, A., Djuric, Z., & Brenner, D. E. (2015). Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer. Molecular Carcinogenesis, 54, 908–915.