Browse > Article
http://dx.doi.org/10.17480/psk.2016.60.3.101

Anticancer Mechanisms of 3-Heptylamino-6-Allylthiopyridazine and 3-Dipentylamino-6-Allylthiopyridazine in Human Colon Carcinoma RKO Cells  

Lim, Hyun Kyung (College of Pharmacy, Duksung Women's University)
Kwon, Yumi (College of Pharmacy, Duksung Women's University)
Song, Jiyun (College of Pharmacy, Duksung Women's University)
Kim, Kyoung Mee (College of Pharmacy, Duksung Women's University)
Kim, Chaewon (College of Pharmacy, Duksung Women's University)
Park, Myung-Sook (College of Pharmacy, Duksung Women's University)
Jung, Joohee (College of Pharmacy, Duksung Women's University)
Publication Information
YAKHAK HOEJI / v.60, no.3, 2016 , pp. 101-106 More about this Journal
Abstract
Allylthiopyridazine derivatives were synthesized and evaluated for anti-proliferative activities in the previous study. In this study, selected two allylthiopyridazine derivatives (compound I, 3-heptylamino-6-allylthiopyridazine and compound II, 3-dipentylamino-6-allylthiopyridazine) were assessed for cytotoxicity and chronic proliferation in human colon carcinoma RKO cells. Two derivatives dose-dependently inhibited cell viability and proliferation. To elucidate the anticancer mechanism of two derivatives, we investigated the expression level of apoptosis-related proteins in RKO cells. Compound I induced the activation of JNK and expression of p53 and p21. On the other hand, compound II showed no change of p53 level. Interestingly, compound II inhibited the nuclear translocation of NF-${\kappa}B$. This result suggested that compound II suppressed cell proliferation. These different mechanisms of these compounds might have occurred through different steric conformation.
Keywords
3-heptylamino-6-allylthiopyridazine; 3-dipentylamino-6-allylthiopyridazine; anticancer effect; RKO cell;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Chanh, P. H., Lasserre, B., Kaiser, R., Couquelet, J., Coudert, P. and Rubat, C. : Aminopyridazine derivatives and TXA2-PGI2 balance. Prostaglandins Leukot. Essent. Fatty Acids 40, 143 (1990).   DOI
2 Zhou, W., Zhong, G., Rao, X., Xie, H., Zeng, S., Chi, T., Zou, L., Wu, D. and Hu, W. : Identification of aminopyridazine-derived antineuroinflammatory agents effective in an Alzheimer's mouse model. ACS Med. Chem. Lett. 3, 903 (2012).   DOI
3 Craft, J. M., Van Eldik, L. J., Zasadzki, M., Hu, W. and Watterson, D. W. : Aminopyridazines attenuate hippocampusdependent behavioral deficits induced by human beta-amyloid in a murine model of neuroinflammation. J. Mol. Neurosci. 24, 115 (2004).   DOI
4 Velentza, A. V., Wainwright, M. S., Zasadzki, M., Mirzoeva, S., Schumacher, A. M., Haiech, J., Focia, P. J., Egli, M. and Watterson, D. M. : An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Bioorg. Med. Chem. Lett. 13, 3465 (2003).   DOI
5 Velentza, A. V., Wainwright, M. S., Zasadzki, M., Mirzoeva, S., Schumacher, A. M., Haiech, J., Focia, P. J., Egli, M. and Watterson D. M. : An aminopyridazin-based inhibitor of a proapoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Bioorg. Med. Chem. Lett. 13, 3465 (2003).   DOI
6 Zhou, W., Zhong, G., Rao, X., Xie, H., Zeng, S., Chi, T., Zou, L., Wu, D. and Hu, W. : Identification of aminopyridazine-derived antineuroinflammatory agents effective in an Alzheimer's mouse model. ACS Med. Chem. Lett. 3, 903 (2012).   DOI
7 Lee, M.-S., Kim, E.-S., Moon, A. and Park, M.-S. : Synthesis of novel allylthio heterocyclo(or aryl)alkylaminopyridazines and tehir anticancer activity against SK-Hep-1 cells. Bull. Korean Chem. Soc. 30, 83 (2009).   DOI
8 Dhanasekaran, D. N. and Reddy, E. P. : JNK signaling in apoptosis. Oncogene 27, 6245 (2008).   DOI
9 Lee, M.-S. and Kim, K.-A. : NF-${\kappa}B$ pathway in metabolic/endocrine diseases. 대한내분비학회지 21, 352 (2006).
10 Murtas, D., Piras, F., Minerba, L., Ugalde, J., Piga, M., Maxia, C., Perra, M. T. and Sirigu, P. : Nuclear factor-${\kappa}B$ expression is predictive of overall survival in patients with cutaneous melanoma. Oncol. Lett. 1, 633 (2010).   DOI
11 Arbab, I. A., Looi, C. Y., Abdul, A. B., Cheah, F. K., Wong, W. F., Sukari, M. A., Abdullah, R., Mohan, S., Syam, S., Arya, A., Mohamed Elhassan Taha, M., Muharram, B., Rais Mustafa, M. and Ibrahim Abdelwahab, S. : Dentatin induces apoptosis in prostate cancer cells via Bcl-2, Bcl-xL, surviving downregulation, caspase-9,-3/7 activation, and NF-${\kappa}B$ inhibition. Evid. Based Complement. Alternat. Med. 2012, 856029 (2012).
12 Ito, Y., Kikuchi, E., Tanaka, N., Kosaka, T., Suzuki, E., Mizuno, R., Shinojima, T., Miyajima, A., Umezawa, K. and Oya, M. : Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer. BMC Cancer 15, 324 (2015).   DOI
13 Feldberg, R. S., Chang, S. C., Kotik, A. N., Nadler, M., Neuwirth, Z., Sundstrom, D. C. and Thompson, N. H. : In vitro mechanism of inhibition of bacterial cell growth by allicin. Antimicrob. Agents Chemother. 32, 1763 (1988).   DOI
14 Wallock-Richards, D., Doherty, C. J., Doherty, L., Clarke, D. J., Place, M., Govan, J. R. W. and Campopiano, D. J. : Garlic revisited: Antimicrobial activity of allicin-containing garilic extracts against Burkholderia cepacia complex. PLoS ONE 9, e112726 (2014).   DOI
15 Tao, M., Gao, L., Pan, J. and Wang, X. : Study on the inhibitory effect of allicin on human gastric cancer cell line SGC-7901 and its mechanism. Afr. J. Tradit. Complement Altern. Med. 11, 176 (2014).
16 Xu, L., Yu, J., Zhai, D., Zhang, D., Shen, W., Bai, L., Cai, Z. and Yu, C. : Role of JNK activation and mitochondrial bax translocation in allicin-induced apoptosis in human ovarian cancer SKOV3 cells. Evid. Based Complement. Alternat. Med. 2014, Article ID 378684 (2014).
17 Borlinghaus, J., Albrecht, F., Gruhlke, M. C. H., Nwachukwu, I. D. and Slusarenko, A. J. : Allicin: Chemistry and biological properties. Molecules 19, 12591 (2014).   DOI
18 Fujisawa, H., Suma, K., Origuchi, K., Kumagai, H., Seki, T. and Ariga, T. : Biological and chemical stability of garlic-derived allicin. J. Agric. Food Chem. 56, 4339 (2008).
19 Kim, C., Park, E.-H. and Park, M.-S. : Novel alkylaminopyridazine derivatives: Synthesis and their anti-proliferative effects against MCF-7 cells. Bull. Korean Chem. Soc. 34, 3317 (2013).   DOI