Summary
The rhenium(I)-diselenoether complex (Re-diSe) is a rhenium tricarbonyl-based drug chelated by a diselenoether ligand. In this work, we compared its inhibitory effects on the hormone-independent MDA-MB231cancer line and other different cancer cell lines after an exposure time of 72 h by MTT assays. The sensitivity of MDA-MB231 was in the same range than the hormone-dependent MCF-7 breast cancer, the PC-3 prostate and HT-29 colon cancer cells, while the A549 lung and the HeLa uterine cancer cells were less sensitive. We compared the inhibitory effects of Re-diSe and of its diselenide ligand (di-Se) on MDA-MB231 and a normal HEK-293 human embryonic cell line, after 72 h and 120 h of exposure. The cytotoxicity was also studied by flow cytometry using ethidium bromide assays, as well as the effects on the ROS production by DFCA-test, while the levels of TGF-β1, VEGF-A, IGF-1 were addressed by ELISA tests. The dose required to inhibit 50% of the proliferation (IC50) of MDA-MB231 breast cancer cells decreased with the time of exposure to 120 h, while the free ligand (di-Se) was found poorly active, demonstrating the important role of Re in this Re-diSe combination. The cytotoxic effects of Re-diSe were highly selective for cancer cells, with a significant increase of the number of dead cancer cells at 5 μM for an exposure time of 120 h, while normal cells were not affected. A remarkable and significant decrease of the production of ROS together with a decrease of VEGF-A, TGF-β1, and IGF-1 by the cancer cells were also observed when cancer cells were exposed to Re-diSe.
Similar content being viewed by others
References
Yardley DA, Coleman R, Conte P, Cortes J, Brufsky A, Shtivelband M, Young R, Bengala C, Ali H, Eakel J, Schneeweiss A, de la Cruz-Merino L, Wilks S, O'Shaughnessy J, Gluck S, Li H, Miller J, Barton D, Harbeck N (2018) Nab-paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial. Ann Oncol 29(8):1763–1770. https://doi.org/10.1093/annonc/mdy201
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast Cancer. N Engl J Med 379(22):2108–2121. https://doi.org/10.1056/NEJMoa1809615
Ferrero JM, Hardy-Bessard AC, Capitain O, Lortholary A, Salles B, Follana P, Herve R, Deblock M, Dauba J, Atlassi M, Largillier R (2016) Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first-line therapy for triple-negative, metastatic, or locally advanced breast cancer: results from the GINECO A-TaXel phase 2 study. Cancer 122(20):3119–3126. https://doi.org/10.1002/cncr.30170
Kermagoret A, Morgant G, D’Angelo J, Tomas A, Roussel P, Bastian G, Collery P, Desmaële D (2011) Synthesis, structural characterization and biological activity against several human tumor cell lines of four rhenium(I) diseleno-ethers complexes: Re(CO)3Cl(PhSe(CH2)2SePh), Re(CO)3Cl(PhSe(CH2)3SePh), Re(CO)3Cl(HO2C–CH2Se(CH2)2SeCH2–CO2H) and Re(CO)3Cl(HO2C–CH2Se(CH2)3SeCH2–CO2H). Polyhedron 30:347–354
Collery P, Bastian G, Santoni F, Mohsen A, Wei M, Collery T, Tomas A, Desmaele D, D’Angelo J (2014) Uptake and efflux of rhenium in cells exposed to rhenium Diseleno-ether and tissue distribution of rhenium and selenium after rhenium Diseleno-ether treatment in mice. Anticancer Res 34:1679–1690
Collery P, Mohsen A, Kermagoret A, Corre S, Bastian G, Tomas A, Wei M, Santoni F, Guerra N, Desmaele D, d'Angelo J (2015) Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer. Investig New Drugs 33(4):848–860. https://doi.org/10.1007/s10637-015-0265-z
Collery P, Santoni F, Ciccolini J, Tran TN, Mohsen A, Desmaele D (2016) Dose effect of rhenium (I)-diselenoether as anticancer drug in resistant breast tumor-bearing mice after repeated administrations. Anticancer Res 36(11):6051–6057
Zhang B, Fang C, Deng D, Xia L (2018) Research progress on common adverse events caused by targeted therapy for colorectal cancer. Oncol Lett 16(1):27–33. https://doi.org/10.3892/ol.2018.8651
Gerson JN, Ramamurthy C, Borghaei H (2018) Managing adverse effects of immunotherapy. Clin Adv Hematol Oncol 16(5):364–374
Marshall HT, Djamgoz MBA (2018) Immuno-oncology: emerging targets and combination therapies. Front Oncol 8(315). https://doi.org/10.3389/fonc.2018.00315
Mencalha A, Victorino VJ, Cecchini R, Panis C (2014) Mapping oxidative changes in breast cancer: understanding the basic to reach the clinics. Anticancer Res 34(3):1127–1140
Alhallak K, Rebello LG, Muldoon TJ, Quinn KP, Rajaram N (2016) Optical redox ratio identifies metastatic potential-dependent changes in breast cancer cell metabolism. Biomed Opt Express 7(11):4364–4374. https://doi.org/10.1364/BOE.7.004364
Bahhnassy A, Mohanad M, Shaarawy S, Ismail MF, El-Bastawisy A, Ashmawy AM, Zekri AR (2015) Transforming growth factor-beta, insulin-like growth factor I/insulin-like growth factor I receptor and vascular endothelial growth factor-a: prognostic and predictive markers in triple-negative and non-triple-negative breast cancer. Mol Med Rep 12(1):851–864. https://doi.org/10.3892/mmr.2015.3560
Ho J, Lee WY, Koh KJ, Lee PP, Yan YK (2013) Rhenium(I) tricarbonyl complexes of salicylaldehyde semicarbazones: synthesis, crystal structures and cytotoxicity. J Inorg Biochem 119:10–20. https://doi.org/10.1016/j.jinorgbio.2012.10.011
Konkankit CC, Marker SC, Knopf KM, Wilson JJ (2018) Anticancer activity of complexes of the third row transition metals, rhenium, osmium, and iridium. Dalton Trans 47:9934–9974. https://doi.org/10.1039/c8dt01858h
Ramakrishna B, Nagarajaprakash R, Veena V, Sakthivel N, Manimaran B (2015) Self-assembly of oxamidato bridged ester functionalised dirhenium metallastirrups: synthesis, characterisation and cytotoxicity studies. Dalton Trans 44(40):17629–17638. https://doi.org/10.1039/c5dt02205c
North AJ, Hayne DJ, Schieber C, Price K, White AR, Crouch PJ, Rigopoulos A, O'Keefe GJ, Tochon-Danguy H, Scott AM, White JM, Ackermann U, Donnelly PS (2015) Toward hypoxia-selective rhenium and technetium tricarbonyl complexes. Inorg Chem 54(19):9594–9610. https://doi.org/10.1021/acs.inorgchem.5b01691
Kumar CA, Nagarajaprakash R, Victoria W, Veena V, Sakthivel N, Manimaran B (2016) Synthesis, characterisation and cytotoxicity studies of manganese(I) and rhenium(I) based metallacrown ethers. Inorg Chem Commun 64:39–44
Parson C, Smith V, Krauss C, Banerjee HN, Reilly C, Krause JA, Wachira JM, Giri D, Winstead A, Mandal SK (2015) Anticancer properties of novel rhenium Pentylcarbanato compounds against MDA-MB-468(HTB-132) triple node negative human breast Cancer cell lines. Br J Pharm Res 4(3):362–367. https://doi.org/10.9734/BJPR/2014/4697
Banerjee HN, Vaughan D, Boston A, Thorne G, Payne G, Sampson J, Manglik V, Olczak P, Powell BV, Winstead A, Shaw R, Mandal SK (2018) The effects of synthesized rhenium acetylsalicylate compounds on human astrocytoma cell lines. J Cancer Sci Ther 10(2). https://doi.org/10.4172/1948-5956.1000512
Diaz M, Gonzalez R, Plano D, Palop JA, Sanmartin C, Encio I (2018) A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells. J Cell Mol Med 22(1):289–301. https://doi.org/10.1111/jcmm.13318
Garnica P, Encio I, Plano D, Palop JA, Sanmartin C (2018) Combined Acylselenourea-Diselenide structures: new potent and selective Antitumoral agents as autophagy activators. ACS Med Chem Lett 9(4):306–311. https://doi.org/10.1021/acsmedchemlett.7b00482
Collery P (2018) Strategies for the development of selenium-based anticancer drugs. J Trace Elem Med Biol 50:498–507. https://doi.org/10.1016/j.jtemb.2018.02.024
Gao X, Schottker B (2017) Reduction-oxidation pathways involved in cancer development: a systematic review of literature reviews. Oncotarget 8(31):51888–51906. https://doi.org/10.18632/oncotarget.17128
Chen X, Song M, Zhang B, Zhang Y (2016) Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxidative Med Cell Longev 2016:1580967–1580910. https://doi.org/10.1155/2016/1580967
Ohl K, Tenbrock K (2018) Reactive oxygen species as regulators of MDSC-mediated immune suppression. Front Immunol 9:2499. https://doi.org/10.3389/fimmu.2018.02499
Zhang Y, Han SJ, Park I, Kim I, Chay KO, Kim SM, Jang DI, Lee TH, Lee SR (2017) Redox regulation of the tumor suppressor PTEN by hydrogen peroxide and Tert-butyl Hydroperoxide. Int J Mol Sci 18(5). https://doi.org/10.3390/ijms18050982
Conrad M, Sandin A, Forster H, Seiler A, Frijhoff J, Dagnell M, Bornkamm GW, Radmark O, Hooft van Huijsduijnen R, Aspenstrom P, Bohmer F, Ostman A (2010) 12/15-lipoxygenase-derived lipid peroxides control receptor tyrosine kinase signaling through oxidation of protein tyrosine phosphatases. Proc Natl Acad Sci U S A 107(36):15774–15779. https://doi.org/10.1073/pnas.1007909107
Garcia CV, Parrilha GL, Rodrigues BL, Teixeira SF, de Azevedo RA, Ferreira AK, Beraldo H (2016) Tricarbonylrhenium(i) complexes with 2-acetylpyridine-derived hydrazones are cytotoxic to NCI-H460 human large cell lung cancer. New J Chem 40(9):7379–7387. https://doi.org/10.1039/C6NJ00050A
Kaur T, Lee WZ, Ravikanth M (2016) Rhenium(I) Tricarbonyl complexes of meso-Tetraaryl-21,23-diheteroporphyrins. Inorg Chem 55(11):5305–5311. https://doi.org/10.1021/acs.inorgchem.6b00214
Ruiz GT, Juliarena MP, Lezna RO, Wolcan E, Feliz MR, Ferraudi G (2007) Intercalation of fac-[(4,4′-bpy)ReI(CO)3(dppz)]+, dppz = dipyridyl[3,2-a:2′3'-c]phenazine, in polynucleotides. On the UV-vis photophysics of the Re(I) intercalator and the redox reactions with pulse radiolysis-generated radicals. Dalton Trans (20):2020–2029. https://doi.org/10.1039/b614970g
Shamelashvili KL, Shtemenko NI, Leus IV, BabIy SO, Shtemenko OV (2016) Changes in oxidative stress intensity in blood of tumor-bearing rats following different modes of administration of rhenium-platinum system. Ukr Biochem J 8:29–36
Zeng L, Li Y, Li T, Cao W, Yi Y, Geng W, Sun Z, Xu H (2014) Selenium-platinum coordination compounds as novel anticancer drugs: selectively killing cancer cells via a reactive oxygen species (ROS)-mediated apoptosis route. Chem Asian J 9(8):2295–2302. https://doi.org/10.1002/asia.201402256
Su JC, Mar AC, Wu SH, Tai WT, Chu PY, Wu CY, Tseng LM, Lee TC, Chen KF, Liu CY, Chiu HC, Shiau CW (2016) Disrupting VEGF-A paracrine and autocrine loops by targeting SHP-1 suppresses triple negative breast cancer metastasis. Sci Rep 6:28888. https://doi.org/10.1038/srep28888
Thielemann A, Baszczuk A, Kopczynski Z, Kopczynski P, Grodecka-Gazdecka S (2013) Clinical usefulness of assessing VEGF and soluble receptors sVEGFR-1 and sVEGFR-2 in women with breast cancer. Ann Agric Environ Med 20(2):293–297
Nair D, Rådestad E, Khalkar P, Diaz-Argelich N, Schröder A, Klynning C, Ungerstedt J, Uhlin M, Fernandes AP (2018) Methylseleninic acid sensitizes ovarian Cancer cells to T-cell mediated killing by decreasing PDL1 and VEGF levels. Front Oncol 8(407). https://doi.org/10.3389/fonc.2018.00407
Ivanovic V, Demajo M, Krtolica K, Krajnovic M, Konstantinovic M, Baltic V, Prtenjak G, Stojiljkovic B, Breberina M, Neskovic-Konstantinovic Z, Nikolic-Vukosavljevic D, Dimitrijevic B (2006) Elevated plasma TGF-beta1 levels correlate with decreased survival of metastatic breast cancer patients. Clin Chim Acta 371(1–2):191–193. https://doi.org/10.1016/j.cca.2006.02.027
Zarzynska JM (2014) Two faces of TGF-beta1 in breast cancer. Mediat Inflamm 2014:141747–141716. https://doi.org/10.1155/2014/141747
Kim S, Lee J, Jeon M, Nam SJ, Lee JE (2015) Elevated TGF-beta1 and -beta2 expression accelerates the epithelial to mesenchymal transition in triple-negative breast cancer cells. Cytokine 75(1):151–158. https://doi.org/10.1016/j.cyto.2015.05.020
Tan AR, Alexe G, Reiss M (2009) Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer? Breast Cancer Res Treat 115(3):453–495. https://doi.org/10.1007/s10549-008-0184-1
Pei Z, Li H, Guo Y, Jin Y, Lin D (2010) Sodium selenite inhibits the expression of VEGF, TGFbeta(1) and IL-6 induced by LPS in human PC3 cells via TLR4-NF-(K)B signaling blockage. Int Immunopharmacol 10(1):50–56. https://doi.org/10.1016/j.intimp.2009.09.020
Santos Bernardes S, Souza-Neto FP, Pasqual Melo G, Guarnier FA, Marinello PC, Cecchini R, Cecchini AL (2016) Correlation of TGF-β1 and oxidative stress in the blood of patients with melanoma: a clue to understanding melanoma progression? Tumor Biol 37:1–9. https://doi.org/10.1007/s13277-016-4967-4
Girnita L, Worrall C, Takahashi S, Seregard S, Girnita A (2014) Something old, something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation. Cell Mol Life Sci 71(13):2403–2427. https://doi.org/10.1007/s00018-013-1514-y
Key TJ, Appleby PN, Reeves GK, Roddam AW (2010) Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 11(6):530–542. https://doi.org/10.1016/s1470-2045(10)70095-4
Peyrat JP, Bonneterre J, Hecquet B, Vennin P, Louchez MM, Fournier C, Lefebvre J, Demaille A (1993) Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur J Cancer 29a(4):492–497
Bartucci M, Morelli C, Mauro L, Ando S, Surmacz E (2001) Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Cancer Res 61(18):6747–6754
Zhou Y, Li S, Li J, Wang D, Li Q (2017) Effect of microRNA-135a on cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung Cancer. Cell Physiol Biochem 42(4):1431–1446. https://doi.org/10.1159/000479207
Fu YF, Liu X, Gao M, Zhang YN, Liu J (2017) Endoplasmic reticulum stress induces autophagy and apoptosis while inhibiting proliferation and drug resistance in multiple myeloma through the PI3K/Akt/mTOR signaling pathway. Oncotarget 8(37):61093–61106. https://doi.org/10.18632/oncotarget.17862
Bibollet-Bahena O, Almazan G (2009) IGF-1-stimulated protein synthesis in oligodendrocyte progenitors requires PI3K/mTOR/Akt and MEK/ERK pathways. J Neurochem 109(5):1440–1451. https://doi.org/10.1111/j.1471-4159.2009.06071.x
Ren G, Ali T, Chen W, Han D, Zhang L, Gu X, Zhang S, Ding L, Fanning S, Han B (2016) The role of selenium in insulin-like growth factor I receptor (IGF-IR) expression and regulation of apoptosis in mouse osteoblasts. Chemosphere 144:2158–2164. https://doi.org/10.1016/j.chemosphere.2015.11.003
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Philippe Collery declares that he is owner of a patent on “Rhenium complexes and their pharmaceutical use ». Vijay Veena, Adhikesavan Harikrishnan and Didier Desmaelec declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Collery, P., Veena, V., Harikrishnan, A. et al. The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers. Invest New Drugs 37, 973–983 (2019). https://doi.org/10.1007/s10637-019-00727-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10637-019-00727-1