Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors

Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam,...

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Autores principales:	Kim I, Song YH, Singh N, Jeong YJ, Kwon JE, Kim H, Cho YM, Kang SC, Chi KW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5493103f7716456ab89cf6ffd68414a4
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spelling	oai:doaj.org-article:5493103f7716456ab89cf6ffd68414a42021-12-02T02:01:32ZAnticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors1178-2013https://doaj.org/article/5493103f7716456ab89cf6ffd68414a42015-08-01T00:00:00Zhttp://www.dovepress.com/anticancer-activities-of-self-assembled-molecular-bowls-containing-a-p-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam, 4Energy Materials Lab, Korea Institute of Energy Research, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3,6-bis(pyridin-3-ylethynyl)phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2,5-dioxido-1,4-benzoquinonato, OTf = triflate) (2), 5,8-dioxido-1,4-naphthoquinonato (3), or 6,11-dioxido-5,12-naphthacenediona (4), resulted in three molecular bowls 5–7 of general formula [{(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study. Keywords: phenanthrene, ruthenium, coordination self-assembly, gastric cancer, Akt/mTORKim ISong YHSingh NJeong YJKwon JEKim HCho YMKang SCChi KWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss Special Issue on diverse applications in Nano-Theranostics, Pp 143-153 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kim I Song YH Singh N Jeong YJ Kwon JE Kim H Cho YM Kang SC Chi KW Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors
description	Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam, 4Energy Materials Lab, Korea Institute of Energy Research, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3,6-bis(pyridin-3-ylethynyl)phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2,5-dioxido-1,4-benzoquinonato, OTf = triflate) (2), 5,8-dioxido-1,4-naphthoquinonato (3), or 6,11-dioxido-5,12-naphthacenediona (4), resulted in three molecular bowls 5–7 of general formula [{(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study. Keywords: phenanthrene, ruthenium, coordination self-assembly, gastric cancer, Akt/mTOR
format	article
author	Kim I Song YH Singh N Jeong YJ Kwon JE Kim H Cho YM Kang SC Chi KW
author_facet	Kim I Song YH Singh N Jeong YJ Kwon JE Kim H Cho YM Kang SC Chi KW
author_sort	Kim I
title	Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors
title_short	Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors
title_full	Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors
title_fullStr	Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors
title_full_unstemmed	Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors
title_sort	anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and ru(ii) acceptors
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/5493103f7716456ab89cf6ffd68414a4
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_version_	1718402776117018624

Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors

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