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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