Benzoin Thiosemicarbazone Inhibits Growth and Triggers Apoptosis in Earlich Ascites Carcinoma Cells through an Intrinsic Pathway

Hossain Mohammad Zakir^1, , Md. Mahmudul Hassan Mondol^2, , Sha Md. Shahan Shahriar³, Md. Amran Hossain¹, Md Abdur Rahim², Amit Kumar Dey², Ruhul Amin², Md. Zamilur Rahman², Arfatun Nahar Chowdhury², Md. Moniruzzaman², Jahanara Khanam⁴, Md Murshed Hasan Sarkar², Shaikh M Mohsin Ali³ and Mele Jesmin³

¹Department of Chemical Engineering, Z. H. Sikder University of Science and Technology, Sharaitpur, Bangladesh

²Bangladesh Council of Scientific and Industrial Research Laboratories, Rajshahi, Bangladesh

³Department of Applied Chemistry and Chemical Engineering, University of Rajshahi, Rajshahi-6205, Bangladesh

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

Cite this paper:
Hossain Mohammad Zakir, Md. Mahmudul Hassan Mondol, Sha Md. Shahan Shahriar, Md. Amran Hossain, Md Abdur Rahim, Amit Kumar Dey, Ruhul Amin, Md. Zamilur Rahman, Arfatun Nahar Chowdhury, Md. Moniruzzaman, Jahanara Khanam, Md Murshed Hasan Sarkar, Shaikh M Mohsin Ali and Mele Jesmin. Benzoin Thiosemicarbazone Inhibits Growth and Triggers Apoptosis in Earlich Ascites Carcinoma Cells through an Intrinsic Pathway. American Journal of Cancer Prevention. 2019; 7(1):1-9. doi: 10.12691/ajcp-7-1-1

Abstract

Anticancer drug development is now an emerging field of research all over the world. In this study we attempt to synthesize a novel, simple, inexpensive and safe chemical agents Benzoin thiosemicarbazone (BTSC) and studied against Ehrlich Ascites Carcinoma (EAC) cells bearing Swiss Albino mice by monitoring in vivo tumor cell growth inhibition, survival time of tumor bearing swiss albino mice. MTT colorimetric assay was done to assess the in vitro effect of the test compound. The intrinsic apoptotic pathway induced by BTSC was evidenced by p53 or tumor protein, B-cell lymphoma 2 (BCL-2), B-cell lymphoma extra-large (BCL-xL), BCL-2 associated X protein (BAX), cleavage of caspase-9 and caspase-3 and poly-ADP ribose polymerase (PARP-1). Reactive oxygen species (ROS) generation after BTSC treatment was determined by 2´, 7´- dicholorodihydrofluorescein diacetate (DCFH-DA) staining. The compound was found to possess pronounced anticancer effect. Maximum cell growth inhibition, enhancement of life span was found 73.53% and 52.17% at the dose of 8 mg/kg (i.p) respectively. The induction of apoptosis by BTSC occurred through an ROS-dependent mitochondria-mediated intrinsic pathway rather than an extrinsic pathway, and was regulated by the BCL-2 protein family. The compound exerted a potent antitumor effect toward Ehrlich ascites carcinoma cells through the induction of apoptosis via an intrinsic pathway. Thus, this study provides evidence to carry out further researches in a way to formulate novel anticancer drugs.

Keywords:
EAC cells benzoin thiosemicarbazone intrinsic pathway ROS caspase inhibitor

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	M. M. Ali, M. A. K. Azad, M. Jesmin, S. Ahsan, M. M. Rahman, J. A. Khanam, “In vivo anticancer activity of vanillin semicarbazone,” Asian Paci J of Tropi Biomed..
[2]	H. M. Zakir, M. K. Islam, M. R. Hasan, M. M. Ali, M. Jesmin M, “In Vivo anticancer activities of Co(II)- Benzoin Thiosemicarbazone Complex [Co(BTSC)2],” International Journal of Biosciences, vol.9, pp.209-220, 2016.
[3]	H. M. Zakir, M. M. Ali, M. Jesmin, “Antibacterial Activities of Benzoin Thiosemicarbazone and its Complexes with Co (II) and Ni (II),” Asian Journal of Medical and Pharmaceutical Researches, vol. 6, pp. 32-40, 2016.
[4]	M. A. Hossain, M. Yamashita, L. B. Vong, Y. Ikeda, Y. Nagasaki, “Silica-installed redox nanoparticles for novel oral nanotherapeutics–improvement in intestinal delivery with anti-inflammatory effects,” Journal of drug targeting, vol.22 (7), pp. 638-47, 2014.
[5]	A. Pandey, D. Dewangan, S. Verma, A. Mishra, R. D. Dubey, “Synthesis of schiff bases of 2-amino-5-aryl-1, 3, 4-thiadiazole and its analgesic, anti-inflammatory, antibacterial and antitubercular activity,” International Journal of Chemical Technology Research, vol.3, pp.178-184, 2011.
[6]	H. M. Zakir, A. M. Islam, K. Nurtaj, M. M. Ali, M. Jesmin, “Pesticidal activities of benzoin thiosemicarbazone and its complexes with Co (II) and Ni (II),” International Journal of Biosciences, vol. 9, pp. 92-100, 2016.
[7]	M. C. Liu, T. S. Lin, P. Penketh, A. C. Sartorelli, “Synthesis and antitumor activity of 4- and 5- substituted derivatives of isoquiniline-1-carboxaldehyde thiosemicarbazone,” Journal of Medicinal Chemistry, vol. 38, pp. 4234-43, 1995.
[8]	M. M. Ali, M. Jesmin, M. K. Islam, K. Fatema, K. A. Azad, “Antineoplastic activities of acetone thiosemicarbazone against Ehrlich ascites carcinoma cells bearing mice,” Medical Journal of Islamic World Academy of Sciences, vol. 21, pp. 97-104, 2013.
[9]	S. M. S. Shahriar, M. M. Ali, M. Jesmin, “In vivo anticancer activities of vanillin thiosemicarbazone Complexes with Co (II) and Ni (II),” Medical Journal of Islamic World Academy of Sciences, vol. 23, pp. 90-95, 2015.
[10]	M. M. Ali, H. M. Zakir, S. M. S. Shahriar, M. H. Sarkar, A. K. Dey, H. P. Nur, “In Vivo anticancer activities of Ni(II)-Benzoin Thiosemicarbazone complex [Ni(BTSC)2] against Ehrlich Ascites Carcinoma cells,” J. Bio-Sci. vol. 23, pp. 77-88. (2015), (Published in June, 2018).
[11]	L. Bai, S. Wang, “Targeting apoptosis pathways for new cancer therapeutics,” Annu.Rev. Med., vol. 65, pp. 139-155, 2014.
[12]	S. W. Tait, D. R. Green, “Mitochondria and cell death; outer membrane permeabilization and beyond,” Nat. Rev. Mol. Cell Biol., vol. 11, pp. 621-632, 2010.
[13]	D. Wallach, T. B. Kang, A. Kovalenko, “The extrinsic cell death pathway and the elan mortel,” Cell death Differ. vol. 15, pp. 1533-1541, 2008.
[14]	M. S. Ola, M. Nawaz, H. Ahsan, “Role of Bcl-2 family proteins and caspases in the regulation of apoptosis,” Mol. Cell. Biochem. vol. 351, pp.41-58, 2011.
[15]	D. R. Mcllwain, T. Berger, W. T. Mak, “Caspase functions in cell death and disease,” Cold spring harbor pers in bio. 2013.
[16]	J. T. Hancock, R. Desikan, S. J. Neill, “Role of reactive oxygen species in cell signaling pathways,” Biochem and biome asp of oxida modification, vol. 29, pp. 345-350, 2001.
[17]	Elementary Practical Organic Chemistry Part-2: Qualilative Organic Analysis, 2nd ed. Longman; 1974.
[18]	M. S. El-Shahawi, M. S. Al-Jahdali, A. S. Bashammakh, A. A. Al-Sibaai, H. M. Nassef, “Spectroscopic and electrochemical characterization of some Schiff base metal complexes containing benzoin moiety,” Acta Part A: Mol and Biom Spectroscopy, vol. 113, pp. 459-465, 2013.
[19]	P. Sur and D. K. Ganguly, “Tea plant root extract (TRE) as an antineoplastic agent,” Planta Medica, vol. 60, pp. 106, 1994.
[20]	B. J. Abbot, “Bioassay of plant extract for anticancer activity,” Cancer Treatment Reports, vol. 60, pp. 1007-1017, 1976.
[21]	S. N. S. A. Rahman, N. W. Wahab, S. N. A. Malek, “In Vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria,” Evid Base Comp Alter Med. 2012; 1-14.
[22]	J. Chun-Ping, D. Hui, S. Da-Hua, W. Yu-Rong, L. Er-Guang, W. Jun-Hua, “Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells,” W. J. Gastro, vol. 18, pp. 1753-1764, 2012.
[23]	W. Yinyuan, W. Dianjun, W. Xiaodong, W. Yinyin, R. Fangli, C. Donald, “Caspase-3 is activated through caspase-8 instead of caspase-9 during H2O2-induced apoptosis in HeLa Cells,” Cell Physical Biochemistry, vol. 27, pp.539-546, 2011.
[24]	W. Xiao-Dong, L. Chen-Yang, J. Miao-Miao, L. Dong, W. Ping, S. Xun, “Induction of apoptosis in human leukemia cells through an intrinsic pathway by cathachunine, a unique alkaloid isolation from Catharanthus roseus,” Phytomedicine, vol. 23, pp. 641-653, 2016.
[25]	A. Gradilone, P. Gazzaniga, D. Ribuffo, “Surviving, bcl-2, bax, and Bcl-X gene expression in sentinel lymph nodes from melanoma patients,” J. Clin Oncol, vol. 21, pp. 306-312, 2003.
[26]	S. R. Kabir, M. M. Nabi, A. Haque, R. Zaman, Z. H. Mahmud, A. M. Reza, “Pea Lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing apoptosis and G2/M cell cycle arrest in vivo in mice,” Phytomedicine, vol. 20, pp.1288-1296, 2013.
[27]	D. R. Green, G. Kroemer, “The pathophysiology of mitochondrial cell death,” Science, vol. 305, pp.626-629, 2004.
[28]	J. R. Stone, T. Collins, “The role of hydrogen peroxide in endothelial proliferative responses,” Endothelium. J. Endothe, cell Res. Vol. 9, pp.231-238, 2002.
[29]	Y. Chen, M. B. Azad, S. B. Gibson, “Superoxide is the major reactive oxygen species regulating autophagy,” Cell death differ, vol. 16, pp.1040-1052, 2009.
[30]	N. J. Holbrook, S. Ikeyama, “Age-related decline in cellular response to oxidative stress; links to growth factor signaling pathways with common defects,” Biochem, Pharmacol, vol. 64, pp.999-1005, 2002.