Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands
autophagy
apoptosis
610
Antineoplastic Agents
Apoptosis
540
Ethylenediamines
Ligands
01 natural sciences
Rats
0104 chemical sciences
3. Good health
Mice
Coordination Complexes
Cell Line, Tumor
cancer
oxidative stress
Animals
Humans
platinum
Cisplatin
Platinum
DOI:
10.1002/cmdc.201000058
Publication Date:
2010-04-20T17:52:38Z
AUTHORS (11)
ABSTRACT
AbstractThe present study describes the synthesis and anticancer activity of novel octahedral PtIV complexes with cyclohexyl functionalized ethylenediamine‐N,N′‐diacetate‐type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s‐cis is the preferred geometry of these PtIV complexes with tetradentate‐coordinated (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell‐cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel PtIV complexes against various cancer cell lines (IC50 range: 1.9–8.7 μM) was higher than that of cisplatin (IC50 range: 10.9–67.0 μM) and proceeded through completely different mechanisms. Cisplatin induced caspase‐dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new PtIV complexes caused rapid, caspase‐independent, oxidative stress‐mediated non‐apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (43)
CITATIONS (47)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....