Abstract:
:The chemotherapeutic drug cisplatin is an important treatment for many types of solid tumours, in particular non-small cell lung cancer (NSCLC). Platinum(IV) complexes offer several advantages to cisplatin due to their requirement for reduction to the active platinum(II) form to elicit cytotoxicity. This should minimise non-specific effects and facilitate higher amounts of the active complexes reaching the target DNA. Hypoxia and a quiescent cell population are features of the tumour microenvironment known to lead to resistance to many chemotherapeutic agents. It is unclear how these microenvironmental factors will impact on the efficacy of novel platinum(IV) complexes. Consequently, the cytotoxicities of several platinum drugs were determined in monolayer and tumour spheroid cultures derived from NSCLC lines. Platinum(IV) reduction potential correlated well with cytotoxicity. The complex containing a chloro axial ligand demonstrated the greatest potency and the drug with the hydroxy ligand was the least effective. Although drug cytotoxicity was not enhanced under hypoxic conditions, both cisplatin and the platinum(IV) complexes retained full potency. In addition, all of the platinum drugs retained the ability to evoke apoptosis in quiescent cells. In summary, unlike many anticancer drugs, the platinum(IV) complexes retain cytotoxic potency under resistance-inducing tumour microenvironmental conditions and warrant further investigation as more selective alternatives to current platinum-based therapy for the treatment of solid tumours.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Mellor HR,Snelling S,Hall MD,Modok S,Jaffar M,Hambley TW,Callaghan Rdoi
10.1016/j.bcp.2005.07.016subject
Has Abstractpub_date
2005-10-15 00:00:00pages
1137-46issue
8eissn
0006-2952issn
1873-2968pii
S0006-2952(05)00488-0journal_volume
70pub_type
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journal_title:Biochemical pharmacology
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