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

Kim I, Song YH, Singh N, Jeong YJ, Kwon JE, Kim H, Cho YM, Kang SC, Chi KW - Int J Nanomedicine (2015)

Bottom Line: The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea.

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, [(η6-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 [{(η6-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.

No MeSH data available.


Related in: MedlinePlus

Loss of the growth-inhibitory activity of bowl 6 following preincubation in AGS cell culture medium.Note: DMSO was used as a control.Abbreviations: DMSO, dimethyl sulfoxide; h, hours.
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f8-ijn-10-143: Loss of the growth-inhibitory activity of bowl 6 following preincubation in AGS cell culture medium.Note: DMSO was used as a control.Abbreviations: DMSO, dimethyl sulfoxide; h, hours.

Mentions: The stability of bowl 6 was examined in DMSO and culture medium (10% fetal bovine serum in Dulbecco’s Modified Eagle’s Medium), using conditions similar to those under which the drug is likely to be handled during the course of biological studies. Bowl 6 (10 μM) was preincubated in the culture medium at 37°C for various periods of time before it was added to the AGS cell culture. As a control experiment, bowl 6 was preincubated in DMSO at 37°C for the same periods of time. As shown in Figure 8, bowl 6 was stable in DMSO for 50 hours at a concentration of 10 μM. After preincubation in the culture medium for 24 hours, the inhibitory rate of bowl 6 decreased by 50%.


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

Kim I, Song YH, Singh N, Jeong YJ, Kwon JE, Kim H, Cho YM, Kang SC, Chi KW - Int J Nanomedicine (2015)

Loss of the growth-inhibitory activity of bowl 6 following preincubation in AGS cell culture medium.Note: DMSO was used as a control.Abbreviations: DMSO, dimethyl sulfoxide; h, hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554412&req=5

f8-ijn-10-143: Loss of the growth-inhibitory activity of bowl 6 following preincubation in AGS cell culture medium.Note: DMSO was used as a control.Abbreviations: DMSO, dimethyl sulfoxide; h, hours.
Mentions: The stability of bowl 6 was examined in DMSO and culture medium (10% fetal bovine serum in Dulbecco’s Modified Eagle’s Medium), using conditions similar to those under which the drug is likely to be handled during the course of biological studies. Bowl 6 (10 μM) was preincubated in the culture medium at 37°C for various periods of time before it was added to the AGS cell culture. As a control experiment, bowl 6 was preincubated in DMSO at 37°C for the same periods of time. As shown in Figure 8, bowl 6 was stable in DMSO for 50 hours at a concentration of 10 μM. After preincubation in the culture medium for 24 hours, the inhibitory rate of bowl 6 decreased by 50%.

Bottom Line: The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea.

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, [(η6-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 [{(η6-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.

No MeSH data available.


Related in: MedlinePlus