Vanadyum bileşiklerinin kanserdeki terapötik uygulamaları

Year 2023, Volume: 28 Issue: 3, 441 - 450, 28.09.2023

Fazilet Gök , Suat Ekin

https://doi.org/10.21673/anadoluklin.1185780

Abstract

Vanadyum (V), çoğu memeli dokusunun endojen bir bileşenidir. Vanadyumun önemi insanlarda ve hayvanlarda hala net olmasa da, daha düşük konsantrasyonlarda mikroorganizmalar, bitkiler ve hayvanlar için gereklidir ve canlı organizmalardaki eksikliği birçok yan etkiyle ilişkilidir. Hücrelerde, vanadat ve fosfatın kısmen benzerliğinden dolayı, vanadyum bileşikleri çok sayıda sinyal yolunu ve transkripsiyon faktörünü aktive etmiştir. Bu da vanadyum bazlı terapötiklerin uygulanmasını güçlendirmiştir. Ancak, bu spesifik olmayan biyo-aktivitenin çeşitli yan etkileri de görülmektedir. Reaktif oksijen türleri oluşturarak oksidatif strese neden olabilir. Vanadyumun insülini taklit etme etkisinden dolayı diyabeti tedavi etmek ve gücü artırmak için çok sayıda hapın ve diğer diyet takviyelerinin bir bileşeni haline gelmiştir. Kan hemoglobini, V eksikliğinden etkilenmez, ancak V eksikliği olan diyetler amino asit metabolizmasını değiştirmeden kreatinin, trigliseritler, β-lipoprotein ve enzim benzeri glutamil transferaz ve sitrat asit döngüsünün aktivitelerini arttırır. Kolesterol düzeylerini, kalp hastalığını, sifilizi, tüberkülozu, anemiyi ve ödemi azalttığı, hemoglobin ve miyoglobinin oksijen afinitesinin artırılmasında rol oynadığı, iyot metabolizması ve tiroid fonksiyonu için gerekli olduğu bildirilmektedir. Kemiklerde kalsiyum birikimini kolaylaştırıp kemik kolajen sentezi ile, osteojenik ve osteoblastik aktivite için gereklidir, diyabetik koşullarda potansiyel bir antioksidan ajan olarak hareket eder. Vanadyum bileşikleri birçok alanda olduğu gibi kanseri tedavi etmede de rol oynar. 20. yüzyılın ortalarında, çeşitli çalışmalar, vanadyum bileşiklerinin kanser hücrelerinin apoptozunu, proliferasyonunu ve dönüşümünü düzenleyen potansiyel ajanlar olarak tanımlamışlardır. Vanadyum bileşikleri, bileşiğinin dozuna ve tipine bağlı olarak hem pro- hem de anti-tümör özellikler sergilemişlerdir. Düşük konsantrasyonlarda vanadyum tümör hücrelerinin çoğalmasını uyarırken, yüksek konsantrasyonlar inhibe edebilmektedirler. Bu derleme makalede, farklı kanser türleri için sentezlenen vanadyum bileşikleri ve bunların terapötik etkilerine değinilmiştir.

Keywords

Kanser, oksidatif stres, vanadyum

Therapeutic applications of Vanadium compounds in cancer

Abstract

Vanadium (V) is an endogenous component of most mammalian tissues. Although the importance of vanadium is still unclear in humans and animals, lower concentrations are required for microorganisms, plants and animals, and its deficiency in living organisms is associated with many adverse effects. In cells, due to the partial similarity of vanadate and phosphate, vanadium compounds have activated numerous signaling pathways and transcription factors. This has strengthened the application of vanadium-based therapeutics. However, various side effects of this non-specific bioactivity are also observed. It can cause oxidative stress by generating reactive oxygen species. Due to the insulin-mimicking effect of vanadium, it has become an ingredient in many pills and other dietary supplements to treat diabetes and increase potency. Blood hemoglobin is not affected by V deficiency, but diets with V deficiency increase the activities of creatinine, triglycerides, β-lipoprotein and the enzyme-like glutamyl transferase and citrate acid cycle without altering amino acid metabolism. It is reported that it reduces cholesterol levels, heart disease, syphilis, tuberculosis, anemia and edema, plays a role in increasing the oxygen affinity of hemoglobin and myoglobin and It is reported that it is necessary for iodine metabolism and thyroid function. It facilitates calcium deposition in bones and is required for bone collagen synthesis, osteogenic and osteoblastic activity, and acts as a potential antioxidant agent in diabetic conditions. Vanadium compounds play a role in treating cancer, as in many areas. In the mid-20th century, several studies identified vanadium compounds as potential agents that regulate apoptosis, proliferation, and transformation of cancer cells. Vanadium compounds exhibited both pro- and antitumor properties depending on the dose and type of compound. While low concentrations of vanadium stimulate the proliferation of tumor cells, high concentrations can inhibit it. In this review article, the synthesized vanadium compounds for different cancer types and their therapeutic effects are discussed.

Keywords

Cancer, oxidative stress, vanadium

References

• Tripathi D, Mani V, Pal RP. Vanadium in Biosphere and Its Role in Biological Processes. Biol Trace Elem Res. 2018;186(1):52-67.
• Pessoa JC, Etcheverry S, Gambino D. Vanadium compounds in medicine. Coord Chem Rev. 2015;301:24-48.
• D’Cruz OJ, Uckun FM. Metvan: a novel oxovanadium(IV) complex with broad spectrum anticancer activity. Expert Opin Investig Drugs. 2002;11(12):1829-36.
• Ghosh P, D’Cruz OJ, Narla RK, Uckun FM. Apoptosis-inducing vanadocene compounds against human testicular cancer. Clin Cancer Res. 2000;6(4):1536-45.
• Ferrer EG, Salinas MV, Correa MJ, et al. Synthesis, characterization, antitumoral and osteogenic activities of quercetin vanadyl(IV) complexes. J Biol Inorg Chem. 2006;11(6):791-801.
• Etcheverry SB, Ferrer EG, Naso L, Rivadeneira J, Salinas V, Williams PA. Antioxidant effects of the VO(IV) hesperidin complex and its role in cancer chemoprevention. J Biol Inorg Chem. 2008;13(3):435-47.
• Ge Y, Zhang Y, Chen Y, et al. Silibinin causes apoptosis and cell cycle arrest in some human pancreatic cancer cells. Int J Mol Sci. 2011;12(8):4861-71.
• Mokhtari MJ, Motamed N, Shokrgozar MA. Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line. Cell Biol Int. 2008;32(8):888-92.
• León IE, Cadavid-Vargas JF, Tiscornia I, et al. Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model. J Biol Inorg Chem. 2015;20(7):1175-91.
• Gruzewska K, Michno A, Pawelczyk T, Bielarczyk H. Essentiality and toxicity of vanadium supplements in health and pathology. J Physiol Pharmacol. 2014;65(5):603-11.
• Rehder D. Implications of vanadium in technical applications and pharmaceutical issues. Inorganica Chimica Acta. 2017;455(Part 2);378-89.
• Panchal SK, Wanyonyi S, Brown L. Selenium, Vanadium, and Chromium as Micronutrients to Improve Metabolic Syndrome. Curr Hypertens Rep. 2017;19(3):10.
• Rozzo C, Sanna D, Garribba E, et al. Antitumoral effect of vanadium compounds in malignant melanoma cell lines. J Inorg Biochem. 2017;174:14-24.
• Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003;3(3):203-16.
• Wick A, Wick W, Hirrlinger J, et al. Chemotherapy-induced cell death in primary cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity. J Neurochem. 2004;91(5):1067-74.
• Screnci D, McKeage MJ. Platinum neurotoxicity: clinical profiles, experimental models and neuroprotective approaches. J Inorg Biochem. 1999;77(1-2):105-10.
• Zhang Y, Wang L, Zeng K, Wang K, Yang X. Vanadyl complexes discriminate between neuroblastoma cells and primary neurons by inducing cell-specific apoptotic pathways. J Inorg Biochem. 2018;188:76-87.
• Bansal SS, Goel M, Aqil F, Vadhanam MV, Gupta RC. Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila). 2011;4(8):1158-71.
• Mahmud M, Piwoni A, Filipczak N, Janicka M, Gubernator J. Long-Circulating Curcumin-Loaded Liposome Formulations with High Incorporation Efficiency, Stability and Anticancer Activity towards Pancreatic Adenocarcinoma Cell Lines In Vitro [published correction appears in PLoS One. 2017 Mar 8;12 (3):e0173728]. PLoS One. 2016;11(12):e0167787. .
• Panda AK, Chakraborty D, Sarkar I, Khan T, Sa G. New insights into therapeutic activity and anticancer properties of curcumin. J Exp Pharmacol. 2017;9:31-45.
• Halevas E, Mavroidi B, Swanson CH, et al. Magnetic cationic liposomal nanocarriers for the efficient drug delivery of a curcumin-based vanadium complex with anticancer potential. J Inorg Biochem. 2019;199:110778.
• Guerrero-Palomo G, Rendón-Huerta EP, Montaño LF, Fortoul TI. Vanadium compounds and cellular death mechanisms in the A549 cell line: The relevance of the compound valence. J Appl Toxicol. 2019;39(3):540-552.
• Kowalski S, Wyrzykowski D, Inkielewicz-Stępniak I. Molecular and Cellular Mechanisms of Cytotoxic Activity of Vanadium Compounds against Cancer Cells. Molecules. 2020;25(7):1757.
• Cunha-de Padua MM, Suter Correia Cadena SM, de Oliveira Petkowicz CL, et al. Toxicity of native and oxovanadium (IV/V) galactomannan complexes on HepG2 cells is related to impairment of mitochondrial functions. Carbohydr Polym. 2017;173:665-75.
• Gonçalves AP, Videira A, Soares P, Máximo V. Orthovanadate-induced cell death in RET/PTC1-harboring cancer cells involves the activation of caspases and altered signaling through PI3K/Akt/mTOR. Life Sci. 2011;89(11-12):371-7.
• León IE, Butenko N, Di Virgilio AL, et al. Vanadium and cancer treatment: antitumoral mechanisms of three oxidovanadium(IV) complexes on a human osteosarcoma cell line. J Inorg Biochem. 2014;134:106-17.
• Wang Q, Liu TT, Fu Y, Wang K, Yang XG. Vanadium compounds discriminate hepatoma and normal hepatic cells by differential regulation of reactive oxygen species. J Biol Inorg Chem. 2010;15(7):1087-97.
• Naso LG, Lezama L, Rojo T, et al. Biological evaluation of morin and its new oxovanadium(IV) complex as antioxidant and specific anti-cancer agents. Chem Biol Interact. 2013;206(2):289-301.
• Martínez Medina JJ, Naso LG, Pérez AL, et al. Apigenin oxidovanadium(IV) cation interactions. Synthesis, spectral, bovine serum albumin binding, antioxidant and anticancer studies. Journal Of Photochemistry And Photobiology A-Chemistry. 2017;344:84–100.
• Leon IE, Di Virgilio AL, Porro V, et al. Antitumor properties of a vanadyl(IV) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 in a human osteosarcoma model: the role of oxidative stress and apoptosis. Dalton Trans. 2013;42(33):11868-80.
• Roy S, Banerjee S, Chakraborty T. Vanadium quercetin complex attenuates mammary cancer by regulating the P53, Akt/mTOR pathway and downregulates cellular proliferation correlated with increased apoptotic events. Biometals. 2018;31(4):647-71.
• Nair RS, Kuriakose M, Somasundaram V, Shenoi V, Kurup MR, Srinivas P. The molecular response of vanadium complexes of nicotinoyl hydrazone in cervical cancers--a possible interference with HPV oncogenic markers. Life Sci. 2014;116(2):90-7.
• León IE, Díez P, Baran EJ, Etcheverry SB, Fuentes M. Decoding the anticancer activity of VO-clioquinol compound: the mechanism of action and cell death pathways in human osteosarcoma cells. Metallomics. 2017;9(7):891-901.
• Banerjee S, Dixit A, Shridharan RN, Karande AA, Chakravarty AR. Endoplasmic reticulum targeted chemotherapeutics: the remarkable photo-cytotoxicity of an oxovanadium(IV) vitamin-B6 complex in visible light [published correction appears in Chem Commun (Camb). 2019 Nov 4;55(85):12877-12878]. Chem Commun (Camb). 2014;50(42):5590-2.
• Pisano M, Arru C, Serra M, et al. Antiproliferative activity of vanadium compounds: effects on the major malignant melanoma molecular pathways. Metallomics. 2019;11(10):1687-99.
• Kowalski S, Hać S, Wyrzykowski D, Zauszkiewicz-Pawlak A, Inkielewicz-Stępniak I. Selective cytotoxicity of vanadium complexes on human pancreatic ductal adenocarcinoma cell line by inducing necroptosis, apoptosis and mitotic catastrophe process. Oncotarget. 2017;8(36):60324-41.
• Meyenberg Cunha-de Padua M, Noleto GR, de Oliveira Petkowicz CL, et al. Hypoxia protects against the cell death triggered by oxovanadium-galactomannan complexes in HepG2 cells. Cell Mol Biol Lett. 2019;24:18.
• Lai MY, Hsiu SL, Tsai SY, Hou YC, Chao PD. Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats. J Pharm Pharmacol. 2003;55(2):205-9.
• Martínez Medina JJ, Naso LG, Pérez AL, Rizzi A, Ferrer EG, Williams PAM. Antioxidant and anticancer effects and bioavailability studies of the flavonoid baicalin and its oxidovanadium(IV) complex. J Inorg Biochem. 2017;166:150-61.
• Li J, Jiang M, Zhou H, et al. Vanadium Dioxide Nanocoating Induces Tumor Cell Death through Mitochondrial Electron Transport Chain Interruption. Glob Chall. 2018;3(3):1800058.
• Li S, Chen Y, Zhu W, et al. Engineered nanoscale vanadium metallodrugs for robust tumor‐specific imaging and therapy. Adv Funct Mater. 2021;31:2010337.