Journal of Cancer Research and Treatment
ISSN (Print): 2374-1996 ISSN (Online): 2374-2003 Website: Editor-in-chief: Jean Rommelaere
Open Access
Journal Browser
Journal of Cancer Research and Treatment. 2018, 6(2), 39-46
DOI: 10.12691/jcrt-6-2-3
Open AccessArticle

Induction of Apoptosis in Ehrlich Ascites Carcinoma Cells Through an Intrinsic Pathway by Ni(II)-benzoin Thiosemicarbazone Complex [Ni(BTSC)2]

Hossain Mohammad Zakir1, , Md. Nazrul Islam2, Murshed Hasan Sarkar3, Amit Kumar Dey3, Ruhul Amin3, Jahanara Khanam4, Mele Jesmin1, Husna Parvin Nur3 and Shaikh M Mohsin Ali1

1Department of Applied Chemistry and Chemical Engineering, University of Rajshahi, Rajshahi-6205, Bangladesh

2Department of Applied Chemistry and Chemical Engineering, University of Chittagong, Chittagong-4331, Bangladesh

3Bangladesh Council of Scientific and Industrial Research, Rajshahi, Bangladesh

4Department of Biochemistry & Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh

Pub. Date: May 29, 2018

Cite this paper:
Hossain Mohammad Zakir, Md. Nazrul Islam, Murshed Hasan Sarkar, Amit Kumar Dey, Ruhul Amin, Jahanara Khanam, Mele Jesmin, Husna Parvin Nur and Shaikh M Mohsin Ali. Induction of Apoptosis in Ehrlich Ascites Carcinoma Cells Through an Intrinsic Pathway by Ni(II)-benzoin Thiosemicarbazone Complex [Ni(BTSC)2]. Journal of Cancer Research and Treatment. 2018; 6(2):39-46. doi: 10.12691/jcrt-6-2-3


Cancer is one of the leading causes of morbidity and mortality through worldwide. Globally cancer recognized as the second leading cause of death. Therefore, the discovery and development of new potent and selective anticancer drugs are of high importance in modern cancer research. The objective of this study was to find out the mechanism through which Ni(II)-benzoin thiosemicarbazone complex exerts its antitumor activity against Ehrlich Ascites Carcinoma (EAC) cells bearing swiss albino mice. Induction of apoptosis in EAC cells was confirmed by observation of nuclear morphology and DNA fragmentation assay. The mRNA expression of several apoptotic genes like B-cell lymphoma 2 (bcl-2), B-cell lymphoma extra-large (bcl-xL) caspase-8, and proapoptotic genes p53 or tumor protein, bcl-2 associated X protein (bax), caspase-9, caspase-3 and poly-ADP ribose polymerase (PARP-1) reveal the induction of apoptosis by Ni(BTSC)2 in EAC cell. Inhibition of Ni(BTSC)2 induced apoptosis by Caspase 3 inhibitor treatment affirmed that the induction of intrinsic apoptosis pathway on EAC cells. Reactive Oxygen Species (ROS) generation after Ni(BTSC)2 treatment confirmed that the induction of apoptosis by Ni(BTSC)2 occurred through an ROS-dependent mitochondria-mediated intrinsic pathway rather than an extrinsic pathway. Thus, this study provides evidence to carry out further researches in a way to formulate novel anticancer drugs.

EAC cells nickel benzoin thiosemicarbazone complex intrinsic pathway ROS caspase inhibitor

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


Figure of 7


[1]  Letai, A.G, “Diagnosing and exploiting cancer's addiction to blocks in apoptosis,” Nature Reviews Cancer, 8. 121–132. 2008.
[2]  Bai, L., Wang, S, “Targeting apoptosis pathways for new cancer therapeutics,” Annu. Rev. Med., 65. 139-155. 2014.
[3]  Tait, S.W., Green, D.R, “Mitochondria and cell death; outer membrane permeabilization and beyond,” Nat. Rev. Mol. Cell Biology, 11. 621-632. 2010.
[4]  Wallach, D., Kang, T.B., Kovalenko, A, “The extrinsic cell death pathway and the elan mortel,” Cell death Differ, 15. 1533-1541. 2008.
[5]  Ola, M.S., Nawaz, M., Ahsan, H, “Role of Bcl-2 family proteins and caspases in the regulation of apoptosis,” Mol. Cell. Biochemistry, 351. 41-58. 2011.
[6]  Mcllwain, D.R., Berger, T., Mak,W.T, “Caspase functions in cell death and disease. Cold spring harbor perspectives in biology,” 2013.
[7]  Hancock, J.T., Desikan, R., Neill, S.J, “Role of reactive oxygen species in cell signaling pathways,” Biochem and biome asp of oxida modification, 29. 345-350. 2001.
[8]  Ali, M.M., Zakir, H.M., Shahriar, S.M.S., Khanam, J.A., Jesmin, M, “In Vivo anticancer activity of Ni(II)-Benzoin Thiosemicarbazone complex [Ni(BTSC)2] against ehrlich ascites carcinoma cells in swiss albino mice,” Inter. J. of bio-sciences. 2017. Communicated.
[9]  Frederick, G.M, Elementary Practical Organic Chemistry Part-2: Qualilative Organic Analysis, 2nd ed., Longman Group Limited, London, 1974. 118.
[10]  El-Shahawi, M.S., Al-Jahdali, M.S., Bashammakh, A.S., Al-Sibaai, A.A., Nassef, H.M, “Spectroscopic and electrochemical characterization of some Schiff base metal complexes containing benzoin moiety,” Acta Part A: Mol and Biom Spectroscopy, 113. 459-465. 2013.
[11]  Rahman, S.N.S.A., Wahab, N.W., Malek, S.N.A, “In Vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria,” Evid Base Comp Alter Med, 1-14. 2012.
[12]  Islam, F., Khatun, H., Khatun, M., Ali, M.M., Khanam, J.A, “Growth inhibition and apoptosis of Ehrlich ascites carcinoma cells by the methanol extract of Eucalyptus camaldulensis,” Pharm Biol, 52. 281-290. 2014.
[13]  Yinyuan, W., Dianjun, W., Xiaodong, W., Yinyin, W., Fangli, R., Donald, C., Zhijie, C., Baoqing, J, “Caspase-3 is activated through caspase-8 instead of caspase-9 during H2O2-induced apoptosis in HeLa Cells,” Cell Physical Biochemistry, 27. 539-546. 2011.
[14]  Xiao-Dong, W., Chen-Yang, L., Miao-Miao, J., Dong, L., Ping, W., Xun, S., Jun-Da, C., Li-Xuan, G., Xiao-Peng, H., Guo-Qiang, L., Jian, Z., Chun-Hua, W., Zhen-Dan, H, “Induction of apoptosis in human leukemia cells through an intrinsic pathway by cathachunine, a unique alkaloid isolation from Catharanthus roseus,” Phytomedicine, 23. 641-653. 2016.
[15]  Sakahira, H., Enari, M., Nagata, S, 1998. “Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis,” Nature. 391(6662):96-9. Erratum in: Nature. 2015 Oct 29, 526 (7575):728.
[16]  Graf, D., Bode, J.G., Haussinger, D, “Caspases and receptor cleavage,” Archives of biochem and biophysics, 462. 162-170. 2007.
[17]  Mcllwain, D.R., Berger, T., Mak, T.W, “Caspase functions in cell death and disease,” Cold spring harb perspect biology, 5. Aoo8656. 2013.
[18]  Philchenkov, A., Zavelevich, M., Kroczak, T.J., Los, M, “Caspases and cancer, mechanism of inactivation and new treatment modalities,” Oncology, 26. 82-97. 2004.
[19]  Gradilone, A., Gazzaniga, P., Ribuffo, D, “Survivin, bcl-2, bax, and Bcl-X gene expression in sentinel lymph nodes from melanoma patients,” Journal of Clin. Oncology, 21. 306-312. 2003.
[20]  Kabir, S.R., Nabi, M.M., Haque, A., Zaman, R., Mahmud, Z.H., Reza, A.M, “Pea Lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing apoptosis and G2/M cell cycle arrest in vivo in mice,” Phytomedicine, 20. 1288-1296. 2013.
[21]  Green, D.R., Kroemer, G, “The pathophysiology of mitochondrial cell death,” Science, 305. 626-629. 2004.
[22]  Stone, J.R., Collins, T, “The role of hydrogen peroxide in endothelial proliferative responses, Endothelium,” J. Endothe cell Research, 9. 231-238. 2002.
[23]  Chen, Y., Azad, M.B., Gibson, S.B, “Superoxide is the major reactive oxygen species regulating autophagy,” Cell death differ, 16. 1040-1052. 2009.
[24]  Holbrook, N.J., Ikeyama, S, “Age-related decline in cellular response to oxidative stress; links to growth factor signaling pathways with common defects,” Biochem, Pharmacology, 64. 999-1005. 2002.