sc-144 and Colorectal-Neoplasms

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.

Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Cytotoxins; Drug Screening Assays, Antitumor; Drug Synergism; Female; Humans; Inhibitory Concentration 50; Injections, Intraperitoneal; Mice; Mice, Nude; Organoplatinum Compounds; Paclitaxel; Pyrazines; Quinoxalines; Xenograft Model Antitumor Assays