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Increasing anticancer effect in vitro and vivo of liposome-encapsulated iridium(III) complexes on BEL-7402 cells.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2021 Dec; Vol. 225, pp. 111622. Date of Electronic Publication: 2021 Oct 02. - Publication Year :
- 2021
-
Abstract
- The studies of iridium (III) complexes as potent anticancer reagents have attracted great attention. Here, a new iridium (III) complex [Ir(bzq) <subscript>2</subscript> (PYIP)](PF <subscript>6</subscript> ) (Ir1, bzq = benzo[h]quinoline, PYIP = 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) was synthesized and its liposomes (Ir1Lipo) was prepared. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the cytotoxic activity of Ir1 and Ir1Lipo on HepG2, SGC-7901, BEL-7402, HeLa, B16, A549 and normal NIH3T3 cells. The complex Ir1 displays no obvious inhibitory effect on the growth of BEL-7402 cells, while the Ir1Lipo shows significant cytotoxic activity on BEL-7402 cells (IC <subscript>50</subscript>  = 2.6 ± 0.03 μM). In further studies, Ir1Lipo induced apoptosis by the mitochondrial pathways, such as increasing intracellular reactive oxygen species (ROS) content and intracellular Ca <superscript>2+</superscript> level, decreasing the mitochondrial membrane potential (MMP). In addition, after incubation with Ir1Lipo, the colony formation of BEL-7402 cells was significantly inhibited. Moreover, flow cytometry was used to detect the impact of Ir1Lipo on cell cycle distribution, and western blot was used to detect the expression of caspases and Bcl-2 (B-cell lymphoma-2) family proteins. Furthermore, Ir1Lipo exhibited significant antitumor activity in vivo with an inhibitory rate of 65.8%. These results indicated that Ir1Lipo induces apoptosis in BEL-7402 cells through intrinsic mitochondrial pathway.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Coordination Complexes chemical synthesis
Coordination Complexes pharmacology
Drug Liberation
Drug Screening Assays, Antitumor
Humans
Iridium chemistry
Membrane Potential, Mitochondrial drug effects
Mice
Mitochondria drug effects
NIH 3T3 Cells
Neoplasms metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Reactive Oxygen Species metabolism
S Phase Cell Cycle Checkpoints drug effects
Xenograft Model Antitumor Assays
Antineoplastic Agents therapeutic use
Coordination Complexes therapeutic use
Drug Carriers chemistry
Liposomes chemistry
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 225
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 34624670
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2021.111622