Transitional metals and metal compounds have been used in versatile platforms for biomedical applications and therapeutic intervention. Severe side effects of anticancer drugs produce an urgent urge to develop new classes of anticancer agents with great potency as well as selectivity. In this background, recent studies demonstrate that monomeric manganese (MnII) thiocyanate complex (MMTC) holds great promise to exert effective antileukemic effects. MMTC was developed by a simple chemical reaction and characterized by elemental analyses, thermal analyses, and Fourier transform infrared (FTIR) spectroscopy. Anti-leukemic efficacy of the developed MMTC was estimated in KG-1A (AML) and K562 (CML) cell lines. Cell viability study, drug uptake assay, cellular redox balance (GSH and GSSG level), nitric oxide (NO) release level, reactive oxygen species (ROS) formation, alteration of mitochondrial membrane potential (MMP), and DNA fragmentation revealed that MMTC was able to produce significant antiproliferative effects on both cell lines at 25?μg?mL?1 without showing any toxicological impact on normal lymphocytes. These findings will enlighten the biomedical application of manganese-based metal complexes as anti-leukemic agents. 1. Introduction Leukemia is a type of cancer of the blood or bone marrow, characterized by an abnormal increase of immature white blood cells called “blasts” [1]. Acute myelogenous leukemia (AML) is a fast growing fatal form of leukemia which produces immature white blood cells, begins in bone marrow cells, and spreads into the blood system. Chronic myelogenous leukemia (CML) is an uncommon type of leukemia, making up about 15% of all the cases of leukemia among adults, results from a somatic mutation in a pluripotential lymphohematopoietic cell, and thereby produces large number of white blood cells [2]. The modern research regarding the development of the metal-based anticancer drugs began with the discovery of the platinum (II) complex cisplatin by Rosenberg in the 1960s [3]. Metal complex or coordination compound is a structure consisting of a central metal atom that remains surrounded by molecules or anions. Transition metal complexes have an esteemed role in antitumor therapy and open a new area of research in the field of medicinal chemistry [4]. Nowadays, metal ion complexes had quickly turned out to be an interesting and attractive compounds in the development of anticancer drugs due to their unique chemical reactivity [5]. This phenomenon has started the development of metal-based drugs with promising pharmacological
References
[1]
Leukemia, Mosby's Medical, Nursing & Allied Health Dictionary, Mosby-Year Book, Maryland Heights, Mo, USA, 4th edition, 1994.
[2]
S. Faderl, M. Talpaz, Z. Estrov, and H. M. Kantarjian, “Chronic myelogenous leukemia: biology and therapy,” Annals of Internal Medicine, vol. 131, no. 3, pp. 207–219, 1999.
[3]
B. Rosenberg, L. VanCamp, J. E. Trosko, and V. H. Mansour, “Platinum compounds: a new class of potent antitumour agents,” Nature, vol. 222, no. 5191, pp. 385–386, 1969.
[4]
S. Rafique, M. Idrees, A. Nasim, H. Akbar, and A. Athar, “Transition metal complexes as potential therapeutic agents,” Biotechnology and Molecular Biology Reviews, vol. 5, no. 2, pp. 38–45, 2010.
[5]
P. C. A. Bruijnincx and P. J. Sadler, “New trends for metal complexes with anticancer activity,” Current Opinion in Chemical Biology, vol. 12, no. 2, pp. 197–206, 2008.
[6]
S. Rafique, M. Idrees, A. Nasim, H. Akbar, and A. Athar, “Transition metal complexes as potential therapeutic agents,” Biotechnology and Molecular Biology Reviews, vol. 5, no. 2, pp. 38–45, 2010.
[7]
A. A. Warra, “Transition metal complexes and their application in drugs and cosmetics-a Review,” Journal of Chemical and Pharmaceutical Research, vol. 3, no. 4, pp. 951–958, 2011.
[8]
U. Jungwirth, C. R. Kowol, B. K. Keppler, C. G. Hartinger, W. Berger, and P. Heffeter, “Anticancer activity of metal complexes: involvement of redox processes,” Antioxidants and Redox Signaling, vol. 15, no. 4, pp. 1085–1127, 2011.
[9]
C. G. Dismukes and J. Reedijk, Bioinorganic Catalysis, Marcel Dekker, New York, NY, USA, 1st edition, 1993.
[10]
D. D. Perrin, W. L. F. Armarigo, and D. R. Perrin, Purification of Laboratory Chemicals, Pergamon Press, Oxford, UK, 2nd edition, 1980.
[11]
T. Ghosh, T. Chattopadhyay, S. Das et al., “Thiocyanate and dicyanamide anion controlled nuclearity in Mn, Co, Ni, Cu, and Zn metal complexes with hemilabile ligand 2-benzoylpyridine,” Crystal Growth and Design, vol. 11, no. 7, pp. 3198–3205, 2011.
[12]
S. Chattopadhyay, S. P. Chakraborty, D. Laha, R. Bara, P. Pramanik, and S. Roy, “Surface-modified cobalt oxide nanoparticles: new opportunities for anti-cancer drug development,” Cancer Nanotechnology, vol. 3, no. 1–6, pp. 13–23, 2012.
[13]
L. Hudson and F. C. Hay, Practical Immunology, Blackwell Publishing, Oxford, UK, 3rd edition, 1989.
[14]
S. K. Mahapatra, S. P. Chakraborty, S. Das, and S. Roy, “Methanol extract of Ocimum gratissimum protects murine peritoneal macrophages from nicotine toxicity by decreasing free radical generation, lipid and protein damage and enhances antioxidant protection,” Oxidative Medicine and Cellular Longevity, vol. 2, no. 4, pp. 222–230, 2009.
[15]
S. K. Sahu, S. K. Mallick, S. Santra, T. K. Maiti, S. K. Ghosh, and P. Pramanik, “In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery,” Journal of Materials Science, vol. 21, no. 5, pp. 1587–1597, 2010.
[16]
S. K. Dey and S. Roy, “Role of GSH in the amelioration of chromium-induced membrane damage,” Toxicological & Environmental Chemistry, vol. 92, no. 2, pp. 261–269, 2012.
[17]
L. U. Ling, K.-B. Tan, H. Lin, and G. N. C. Chiu, “The role of reactive oxygen species and autophagy in safingol-induced cell death,” Cell Death and Disease, vol. 2, no. 3, 2011.
[18]
N. Zamzami, C. Maisse, D. Métivier, and G. Kroemer, “Measurement of membrane permeability and the permeability transition of mitochondria,” Methods in Cell Biology, vol. 80, pp. 327–340, 2007.
[19]
S. Kar Mahapatra, S. P. Chakraborty, S. Majumdar, B. G. Bag, and S. Roy, “Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine peritoneal macrophages in vitro,” European Journal of Pharmacology, vol. 623, no. 1–3, pp. 132–140, 2009.
[20]
Bruker, SMART, SAINT. Software Reference Manual, Bruker AXS, Madison, Wis, USA, 2000.
[21]
G. M. Sheldrick, “A short history of SHELX,” Acta Crystallographica Section A, vol. 64, no. 1, pp. 112–122, 2007.
[22]
A. Dhawan, M. A. Kayani, J. M. Parry, E. Parry, and D. Anderson, “Aneugenic and clastogenic effects of doxorubicin in human lymphocytes,” Mutagenesis, vol. 18, no. 6, pp. 487–490, 2003.
[23]
C. L. Chen, X. F. Zhu, M. X. Li, H. M. Guo, and J. Y. Niu, “Antitumor activity of manganese(II) and cobalt(III) complexes of 2-acetylpyridine schiff bases derived from S-methyldithiocarbazate: synthesis, characterization, and crystal structure of the manganese(II) complex of 2-acetylpyridine S-methyldithiocarbazate,” Russian Journal of Coordination Chemistry, vol. 37, no. 6, pp. 435–438, 2011.
[24]
G. N. Ramesh, Y. Subba Rao, B. Prathima, V. Sravani, and A. Varada Reddy, “Synthesis, characterization and biological activities of manganese (II) complex: molecular modeling of DNA interactions,” Der Pharmacia Lettre, vol. 4, no. 4, pp. 1299–1307, 2012.
[25]
E. Besic Gyenge, X. Darphin, A. Wirth et al., “Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma,” Journal of Nanobiotechnology, vol. 9, p. 32, 2011.
[26]
S. Tripathy, S. Das, S. P. Chakraborty, S. K. Sahu, P. Pramanik, and S. Roy, “Synthesis, characterization of chitosan-tripolyphosphate conjugated chloroquine nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: a dose and duration dependent approach,” International Journal of Pharmaceutics, vol. 434, no. 1-2, pp. 292–305, 2012.
[27]
S. H. Snyder and D. S. Bredt, “Nitric oxide as a neuronal messenger,” Trends in Pharmacological Sciences, vol. 12, no. 4, pp. 125–128, 1991.
[28]
H. Ischiropoulos, M. F. Beers, S. T. Ohnishi, D. Fisher, S. E. Garner, and S. R. Thom, “Nitric oxide production and perivascular tyrosine nitration in brain after carbon monoxide poisoning in the rat,” Journal of Clinical Investigation, vol. 97, no. 10, pp. 2260–2267, 1996.
[29]
K. J. Davies, “An overview of oxidative stress,” IUBMB Life, vol. 50, no. 4-5, pp. 241–244, 2000.
[30]
S. K. Sohaebuddin, P. T. Thevenot, D. Baker, J. W. Eaton, and L. Tang, “Nanomaterial cytotoxicity is composition, size, and cell type dependent,” Particle and Fibre Toxicology, vol. 7, p. 22, 2010.
[31]
C. Adrie, M. Bachelet, M. Vayssier-Taussat et al., “Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis,” American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 3, pp. 389–395, 2001.
[32]
L. S. Yazan, F. H. Ahmad, O. C. Li, R. A. Rahim, H. A. Hamid, and L. P. Sze, “Betulinic acid was more cytotoxic towards the human breast cancer cell line MDA-MB-231 than the human promyelocytic leukaemia cell line HL-60,” Malaysian Journal of Pharmaceutical Sciences, vol. 7, no. 1, pp. 23–37, 2009.