Sains Malaysiana 49(6)(2020): 1359-1370

http://dx.doi.org/10.17576/jsm-2020-4906-14

 

Zerumbone Induces Cytotoxicity and Inhibits Cell Migration of Human Colon Cancer Cells

(Zerumbon Mengaruh Kesitotoksikan dan Merencat Penghijrahan Sel pada Sel Kanser Kolon Manusia)

 

TAN MIN JIEN1, SITI NUR PARVIN AB HAMID1, NUR FARIESHA MD HASHIM1, NURDIN ARMANIA1,2, HASNI IDAYU SAIDI1 & NORAINA MUHAMAD ZAKUAN1*

 

1Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

 

2Department of UPM-MAKNA Cancer Research (CANRES), Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

 

Received: 9 December 2019/Accepted: 26 February 2020

 

ABSTRACT

Colon cancer is the second leading cause of cancer death among males and females. Survival in colorectal cancer patients is poor and greatly affected by its metastasis. Zerumbone (ZER) is an active compound isolated from the essential volatile oil of an edible ginger plant, Zingiber zerumbet. It is known to exhibit anticancer properties which able to inhibit cancer cell proliferation and induce apoptosis in colon cancer. These findings led us to investigate the ability of ZER to inhibit cell migration in colon cancer cell line. From the MTT results, the IC50 values for HCT116 cells treated with ZER were 8.9 ± 0.3, 18.0 ± 1.2, and 21.3 ± 3.5 µg/mL at 24, 48, and 72 h of incubation, respectively. The results show that the IC50 was significantly increased (p <0.05) in a time-dependent manner. The treatment of ZER at higher concentration (6 and 9 µg/mL) inhibited the migration of HCT116 cells at 1.5-fold higher compared to that of the untreated cells which reduced in the scratch gap. The characteristic of apoptosis such as cell shrinkage, membrane blabbing, and detachment of cells were observed on HCT116 cells treated with ZER, suggesting that the mode cell death induced by ZER on HCT116 cells might be due to apoptosis. Hence, it is concluded that ZER exhibits cytotoxic effects and inhibits cell migration in colon cancer cells.

 

Keywords: Colon cancer; metastasis; migration; Zerumbone

 

ABSTRAK

Kanser kolon merupakan penyebab kematian kanser kedua dalam kalangan lelaki dan wanita. Jangka hayat pesakit kanser kolorektal adalah rendah dan sangat terjejas disebabkan oleh metastasis. Zerumbon (ZER) adalah sebatian aktif yang dipencil daripada minyak pati halia yang boleh dimakan, Zingiber zerumbet. Ia dipercayai mempunyai sifat antikanser yang dapat merencat percambahan sel kanser dan mengaruh apoptosis. Penemuan ini membawa kami untuk mengkaji keupayaan ZER untuk merencat penghijrahan sel  kanser kolon. Daripada hasil asai MTT, nilai IC50 untuk sel HCT116 yang dirawat dengan ZER adalah 8.9 ± 0.3 μg/mL (24 jam), 18.0 ± 1.2 μg/mL (48 jam) dan 21.3 ± 3.5 μg/mL (72 jam). Keputusan ini menunjukkan bahawa IC50 meningkat dengan ketara (p <0.05) bergantung dengan masa. Rawatan ZER pada kepekatan yang lebih tinggi (6 dan 9 μg/mL) merencat penghijrahan sel HCT116 pada tahap 1.5 kali lebih tinggi berbanding dengan sel yang tidak dirawat yang mana saiz ruang lebih mengecil. Ciri-ciri apoptosis seperti pengecutan sel, pembleban membran dan penanggalan sel diperhatikan pada sel HCT116 yang dirawat dengan ZER, menunjukkan bahawa mod kematian terhadap sel HCT116 yang dirawat dengan ZER mungkin disebabkan oleh apoptosis. Oleh itu, disimpulkan bahawa ZER menunjukkan kesan sitotoksik dan merencat penghijrahan sel kanser kolon.

 

Kata kunci: Kanser kolon; metastasis; penghijrahan; Zerumbon

 

REFERENCES

Abdalla, E.K., Adam, R., Bilchik, A.J., Jaeck, D., Vauthey, J.N. & Mahvi, D. 2006. Improving resectability of hepatic colorectal metastases: Expert consensus statement. Annals Surgical Oncology 13(10): 1271-1280.

Alhumaid, A., Al Yousef, Z., Bakhsh, H.A., AlGhamdi, S. & Aziz, M.A. 2018. Emerging paradigms in the treatment of liver metastases in colorectal cancer. Critical Reviews in Oncology/Hematology 132(2018): 39-50.

Bahuguna, A., Khan, I., Bajpai, V.K. & Kang, S.C. 2017. MTT assay to evaluate the cytotoxic potential of a drug. Bangladesh Journal of Pharmacology 12(2): 115-118.

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. & Jemal, A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 68(6): 394-424.

Cheng, Y., Yang, H., Chen, G. & Zhang, Z. 2013. Molecularly targeted drugs for metastatic colorectal cancer. Drug Design, Development and Therapy 7: 1315-1322.

Deorukhkar, A., Ahuja, N., Mercado, A.L., Diagaradjane, P., Raju, U., Patel, N., Mohindra, P., Diep, N., Guha, S. & Krishnan, S. 2015. Zerumbone increases oxidative stress in a thiol-dependent ROS-independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation. Cancer Medicine 4(2): 278-292.

Fernald, K. & Kurokawa, M. 2013. Evading apoptosis in cancer. Trends in Cell Biology 23(12): 620-633.

Han, J., Bae, S.Y., Oh, S.J., Lee, J., Lee, J.H., Lee, H.C., Lee, S.K., Kil, W.H., Kim, S.W., Nam, S.J., Kim, S. & Lee, J.E. 2014. Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells. Phytotherapy Research 28(11): 1654-1660.

Hoffman, A., Spetner, L.M. & Burke, M. 2002. Redox-regulated mechanism may account for zerumbone’s ability to suppress cancer-cell proliferation. Carcinogenesis 23(11): 1961-1962.

Hosseini, N., Khoshnazar, A., Saidijam, M., Azizi Jalilian, F., Najafi, R., Mahdavinezhad, A., Ezati, R., Sotanian, A. & Amimi, R. 2019. Zerumbone suppress human colorectal cancer invasion and metastasis via modulation of FAk/PI3k/NFκB-uPA pathway. Nutrition and Cancer 71(1): 159-171.

Hosseinpour, M., Abdul, A.B., Rahman, H.S., Rasedee, A., Yeap, S.K., Ahmadi, N., Othman, H.H. & Chartrand, M.S. 2014. Comparison of apoptotic inducing effect of zerumbone and zerumbone-loaded nanostructured lipid carrier on human mammary adenocarcinoma MDA-MB-231 cell line. Journal of Nanomaterials 2014: 1-10.

Kerr, J.F.R., Wyllie, A.H. & Currie, A.R. 1972. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26(4): 239-257.

Kanduc, D., Mittelman, A., Serpico, R., Sinigaglia, E., Sinha, A.A., Natale, C., Santacroce, R., Di Corcia, M.G., Lucchese, A., Dini, L., Pani, P., Santacroce, S., Simone, S., Bucci, R. & Farber, E. 2002. Cell death: Apoptosis versus necrosis (review). International Journal of Oncology 21(1): 165-170.

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.

Liu, X., Yang, W., Guan, Z., Yu, W., Fan, B., Xu, N. & Liao, D.J. 2018. There are only four basic modes of cell death, although there are many ad‑hoc variants adapted to different situations. Cell & Bioscience 8(1): 1-12.

Mahajan, S.D., Law, W.D., Aalinkeel, R., Reynolds, J., Nair, B.B., Yong, K.T., Roy, I., Prasad, P.N. & Schwartz, S.A. 2012. Nanoparticle-mediated targeted delivery of antiretrovirals to the brain. Methods in Enzymology 509: 41-60.

Manan, A.A., Tamin, N.S.I., Abdullah, N.S., Abidin, A.Z. & Wahab, M. 2016. Malaysian National Cancer Registry Report 2007-2011. Putrajaya: Ministry of Health, Malaysia. pp. 1-228.

Nikoletopoulou, V., Markaki, M., Palikaras, K. & Tavernarakis, N. 2013. Crosstalk between apoptosis, necrosis and autophagy. Biochimica et Biophysica Acta 1833(12): 3448-3459.

Rejmontová, P., Capáková, Z., Mikušová, N., Maráková, N., Kašpárková, V., Lehocký, M. & Humpolíček, P. 2016. Adhesion, proliferation and migration of NIH/3T3 cells on modified polyaniline surfaces. International Journal of Molecular Sciences 17(9): 1439.

Shamoto, T., Matsuo, Y., Shibata, T., Tsuboi, K., Nagasaki, T., Takahashi, H., Funahashi, H., Okada, Y. & Takeyama, H. 2014. Zerumbone inhibits angiogenesis by blocking NF-κB activity in pancreatic cancer. Pancreas 43(3): 396-404.

Siegel, R.L., Miller, K.D., Fedewa, S.A., Ahnen, D.J., Meester, R.G.S., Barzi, A. & Jemal, A. 2017. Colorectal cancer statistics, 2017. CA: A Cancer Journal for Clinicians 67(3): 177-193.

Singh, S.P., Nongalleima, K., Singh, N.I., Doley, P., Singh, C.B., Singh, T.R. & Sahoo, D. 2018. Zerumbone reduces proliferation of HCT116 colon cancer cells by inhibition of TNF-alpha. Scientific Reports 8(1): Article ID. 4090.

Sulaiman, M.R., Perimal, E.K., Zakaria, Z.A., Mokhtar, F., Akhtar, M.N., Lajis, N.H. & Israf, D.A. 2009. Preliminary analysis of the antinociceptive activity of zerumbone. Fitoterapia 80(4): 230-232.

Sung, B., Jhurani, S., Ahn, K.S., Mastuo, Y., Yi, T., Guha, S., Liu, M. & Aggarwal, B.B. 2008. Zerumbone down-regulates chemokine receptor CXCR4 expression leading to inhibition of CXCL12-induced invasion of breast and pancreatic tumor cells. Cancer Research 68(21): 8938-8944.

Takada, Y., Murakami, A. & Aggarwal, B.B. 2005. Zerumbone abolishes NF-κB and IκB alpha kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion. Oncogene 24(46): 6957-6969.

Thiyam, R. & Narasu, M.L. 2017. Evaluation of cytotoxic and genotoxic effects of Zerumbone on colon adenocarcinoma COLO205 cells and human lymphocytes. International Journal of Pharmacy and Pharmaceutical Sciences 9(11): 92-96.

Tolosa, L., Donato, M.T. & Gómez-Lechón, M.J. 2015. General cytotoxicity assessment by means of the MTT assay. Methods in Molecular Biology 1250: 333-348.

Vassos, N. & Piso, P. 2018. Metastatic colorectal cancer to the peritoneum: Current treatment options. Current Treatment Options in Oncology 19(10): 1-18.

Wang, M., Niu, J., Gao, L., Gao, Y. & Gao, S. 2019. Zerumbone inhibits migration in ESCC via promoting Rac1 ubiquitination. Biomedicine and Pharmacotherapy 109: 2447-2455.

Yodkeeree, S., Sung, B., Limtrakul, P. & Aggarwal, B.B. 2009. Zerumbone enhances TRAIL-induced apoptosis through the induction of death receptors in human colon cancer cells: Evidence for an essential role of reactive oxygen species. Cancer Research 69(16): 6581-6589.

Zhang, S., Liu, Q., Liu, Y., Qiao, H. & Liu, Y. 2012. Zerumbone, a Southeast Asian ginger sesquiterpene, induced apoptosis of pancreatic carcinoma cells through p53 signaling pathway. Evidence-based Complementary and Alternative Medicine 2012: 1-8.

 

*Corresponding author; email: noraina@upm.edu.my

 

 

 

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