Novel Cyanoximate Pt (DECO)2 as an Anti-Cancer Drug Using ML1 Thyroid Cancer Cells
Rizvanovic Husref and Kim Kyoungtae*
Department of Biology, Missouri State University, Springfield, Missouri, USA
*Corresponding Author: Kim Kyoungtae, Department of Biology, Missouri State University, Springfield, Missouri, USA.
Received: May 20, 2021 ; Published: June 11, 2021
Although current therapies for treating thyroid cancer offers good prognosis, there is an unmet need for better alternative anti-cancer drugs for treatment. Studies have shown that platinum based chemicals such as Cisplatin offer decent treatment options, but can also lead to severe side effects as well as develop a resistance. Given that cyanoximes are great ligands and that metals such as platinum offer good anti-proliferative and cytotoxic abilities, we investigated the role of a novel platinum-based cyanoximate in the treatment of thyroid cancer. Stage 4 thyroid cancer cell line, ML-1, was used in the present study to test the effects on cell viability and proliferation after treatment of Cisplatin and Pt(DECO)2. Changes in the levels of superoxide were also tested and compared with non-treated cells. Lastly, presentation of cell death was recorded after the treatment. After 24 hours of treatment at concentrations of 1.0 mM of Pt(DECO)2, we noticed drastic reduction in cell viability (F = 45.77, p < 0.0001), superoxide levels (F = 28.57, p = 0.0001), and an increase in cell death. These results suggest that this cyanoximate-induced cell death may work similarly to Cisplatin-based cell death. This in vitro study demonstrated the efficacy of the novel cyanoximate Pt(DECO)2 in treating thyroid cancer. Further studies are needed to delineate the effectiveness of this treatment in vivo and with other cancer cell lines.
Keywords: Cisplatin; Platinum; Pt(DECO)2; Thyroid Cancer; ML-1; Apoptosis; ROS; XTT
- Morris LG., et al. “The increasing incidence of thyroid cancer: the influence of access to care”. Thyroid 23 (2013): 885-891.
- Rahib L., et al. “Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the united states”. Cancer Research 11 (2014): 2913-2921.
- Nickel B., et al. “Health-Related Quality of Life After Diagnosis and Treatment of Differentiated Thyroid Cancer and Association With Type of Surgical Treatment”. JAMA Otolaryngology - Head and Neck Surgery 3 (2019): 231-238.
- Schlumberger M., et al. “Lenvatinib versus Placebo in Radioiodine Refractory Thyroid Cancer”. The New England Journal of Medicine 7 (2015): 621-630.
- Schlumberger M., et al. “Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma”. The Journal of Clinical Endocrinology and Metabolism 4 (1986): 960-967.
- Frezza M., et al. “Novel Metals and Metal Complexes as Platforms for Cancer Therapy”. Current Pharmaceutical Design 16 (2010): 18131825.
- Yimit A., et al. “Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs”. Nature Communication 10 (2019): 309.
- Eddings D., et al. “First Bivalent Palladium and Platinum Cyanoximates: Synthesis, Characterizations, and Biological Activity”. Inorganic Chemistry 13 (2004): 3894-3909.
- Dasari S and Tchounwou PB. “Cisplatin in Cancer Therapy: Molecular Mechanisms of Action”. European Journal of Pharmacology 740 (2014): 364-378.
- Bergamo A and Sava G. “Linking the future of anticancer metal-complexes to the therapy of tumour metastases”. Chemical Society Reviews 24 (2015): 8818-8835.
- Ndagi U., et al. “Metal complexes in cancer therapy - an update from drug design perspective”. Drug Design, Development and Therapy 11 (2017): 599-616.
- Ratcliff J., et al. “Part 1: Experimental and theoretical studies of 2-cyano-2-isonitroso- N-piperidynylacetamide (HPiPCO), 2-cyano-2-isonitroso- N-morpholylacetamide (HMCO) and their Pt- and Pdcomplexes”. Inorganica Chimica Acta 285 (2012): 1-20.
- Dannen SD., et al. “New in vitro highly cytotoxic platinum and palladium cyanoximates with minimal side effects in vivo”. Journal of Inorganic Biochemistry (2020) :208.
- Piccinini F., et al. “Cell counting and viability assessment of 2d and 3d cell cultures: expected reliability of the trypan blue assay”. Biological Procedures Online1 (2017): 8.
- Yusof F., et al. “Antioxidants effects of Platinum Nanoparticles: A Potential Alternative Treatment to Lung diseases”. Journal of Applied Pharmaceutical Science 7 (2015): 140-145.
- B Halliwell. “Antioxidants in human health and disease”. Annual Review of Nutrition 6 (1996): 33-50.
- Shibuya S., et al. “Palladium and Platinum Nanoparticles Attenuate Aging- Like Skin Atrophy Via Antioxidant Activity in Mice”. PloS One10 (2014): 109-288.
- Li R., et al. “Defining ROS in Biology and Medicine”. Reactive Oxygen Species (Apex) 1.1 (2016): 9-21.
- Takamiya M., et al. “Neurological and Pathological Improvements of Cerebral Infarction in Mice with Platinum Nanoparticles”. Journal of Neuroscience Research7 (2011): 1125-1133.
- Goldar S., et al. “Molecular mechanisms of apoptosis and roles in cancer development and treatment”. Asian Pacific Journal of Cancer Prevention 6 (2015): 2129-2144.
- Danial NN and Korsmeyer SJ. “Cell Death: Critical Control Points”. Cell 2 (2004): 205-219.
- Pfeffer CM and Singh ATK. “Apoptosis: A Target for Anticancer Therapy”. International Journal of Molecular Sciences 2 (2018): 448.
- Gong C., et al. “Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice”. BMC Complementary and Alternative Medicine 15 (2015): 283.