A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.
Chembiochem
; 25(12): e202400105, 2024 Jun 17.
Article
in En
| MEDLINE
| ID: mdl-38639074
ABSTRACT
Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with inâ
situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both inâ
vitro and inâ
vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Platinum
/
Cellular Senescence
/
Ethylenediamines
/
Aluminum
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Chembiochem
Journal subject:
BIOQUIMICA
Year:
2024
Type:
Article