Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

Drug Design, Development and Therapy Dovepress open access to scientific and medical research Original Research Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 54.38.22.117 on 13-Jul-2018 For personal use only. Open Access Full Text Article Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells This article was published in the following Dove Press journal: Drug Design, Development and Therapy 23 November 2015 Number of times this article has been viewed Somayeh Fani 1 Behnam Kamalidehghan 1 Kong Mun Lo 2 Najihah Mohd Hashim 1 Kit May Chow 2 Fatemeh Ahmadipour 1 Department of Pharmacy, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia 1 Introduction Correspondence: Behnam Kamalidehghan Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran-Karaj Highway, Tehran, 1497716316, Iran Tel +98 21 4478 7301 Fax +98 21 4478 7399 Email Organotin derivatives are one of the many non-platinum metal-based antitumor agents that appear to be very promising as potential drug candidates.1 In recent years, investigations have been carried out to test the cytotoxicity and antitumor activity of organotin (IV) compounds with Schiff bases.2,3 Organotin compounds are found to exhibit good to high cytotoxicity against various human cancer cell lines and are often more potent than cisplatin.4–8 In general, the biochemical activity of organotin compounds is influenced by the structure of the resulting compounds and the nature and number of organic groups bound to the tin center.9–15 In addition, the choice of coordinated ligand is also imperative in the biological effects of organotin compounds, such as solubility and bioavailability. A judicious choice of coordinating ligand not only can minimize the drawbacks, but also can enhance or modulate the activity of organotin compounds,16 as the ligand plays the key role in transporting and directing the molecule to the target site.17 6191 submit your manuscript | www.dovepress.com Drug Design, Development and Therapy 2015:9 6191–6201 Dovepress © 2015 Fani et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/DDDT.S87064 Powered by TCPDF (www.tcpdf.org) Abstract: A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was .30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/ propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells. Keywords: organotin derivatives, apoptosis, MCF-7 cells Dovepress Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 54.38.22.117 on 13-Jul-2018 For personal use only. Fani et al Breast cancer is the most frequent form of cancer and the second most prominent cause of death in women worldwide.18 It is a malignant tumor that develops from breast tissue including ducts and lobule glands, which provide milk to ducts.19,20 Undesirable side effects of current cancer chemotherapeutic and multidrug resistance lead to an increasing interest toward investigating new anticancer agents, including synthetic compounds, with limited toxicity to normal tissue and less multidrug resistance of tumor cells.20,21 Numerous synthetic compounds have demonstrated significant anticancer effects toward breast cancer by targeting various molecular and cellular factors that are involved in the apoptosis mechanism.22,23 Apoptosis, or programmed cell death, acts as a part of normal cell growth in response to diverse extracellular or intracellular stimuli.24 It is vital for tissue homeostasis maintenance via eradicating cells that are no longer needed or are a threat to the organism. It is also necessary in controlling the balance between cell division and cell death, as imbalance between them can cause cancer.25 Defects in this regulated cell suicide process contribute to resistance of tumors, therefore understanding of apoptosis regulation is a key factor in additional promising anticancer drug discovery that can provoke death in cancer cells.26 Increasing evidence has supported that reactive oxygen species (ROS) play a central role in cell signaling and homeostasis.27 Extreme amounts of ROS can cause oxidative damage to lipids, proteins, and DNA, which results in cell death.28 Apoptotic cell death is discovered principally by ladder formation as a result of nuclear DNA degradation into nucleosomal units.29,30 The present work is designed to evaluate the cytotoxic effects and possible mechanisms for the antiproliferative property of compound C1 on human breast cancer MCF-7 cells. We present the apoptosis response of our novel drug by evaluating cell morphological changes, ROS level alteration, an (...truncated)