Combination effects of SC144 and cytotoxic anticancer agents.

Abstract:

:Previously, we synthesized a series of hydrazide class of compounds and examined their cytotoxicity in a number of cancer cell lines. Among these analogues, SC144 exhibited potent cytotoxicity against a panel of drug-sensitive and drug-resistant cancer cell lines. To further explore its therapeutic potentials in the combination settings, we evaluated the synergy between SC144 and selected conventional chemotherapeutic agents in in-vitro cancer cell models. SC144 showed synergism with both 5-fluorouracil and oxaliplatin when cotreated in colorectal cancer HT29 cells. Pretreatment with SC144 in oxaliplatin-resistant HTOXAR3 cells was more effective than oxaliplatin pretreatment. In addition, the combination of SC144 and paclitaxel exhibited synergism in MDA-MB-435 cells with a schedule-dependent block in cell cycle. In an MDA-MB-435 mouse xenograft model, coadministration of SC144 and paclitaxel delayed tumor growth in an SC144 dose-dependent manner. Evaluation of the pharmacokinetics of SC144 revealed that intraperitoneal administration of SC144 showed a two-compartmental pharmacokinetics elimination profile that was not observed in the oral dosing. In summary, these studies further validate SC144 as a novel anticancer agent and provide insights for developing combination therapies for both drug-sensitive and drug-resistant cancers.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Oshima T,Cao X,Grande F,Yamada R,Garofalo A,Louie S,Neamati N

doi

10.1097/CAD.0b013e328323a7ca

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

312-20

issue

5

eissn

0959-4973

issn

1473-5741

journal_volume

20

pub_type

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