Transport and killing mechanism of a novel camptothecin-deoxycholic acid derivate on hepatocellular carcinoma cells. (11th April 2014)

• Record Type: Journal Article
• Authors: Li, Qingyong; Liu, Tianyu; Li, Yunchao; Luo, Shuyue; Zhu, Qiaochu; Zhang, Li; Zhao, Tengfei
• Is Part Of: Journal of drug targeting. Volume 22:Number 6(2014)
• Page Start: 543
• Page End: 552
• Publication Date: 2014-04-11
• Subjects: Apoptosis -- camptothecin -- deoxycholic acid -- uptake; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.3109/1061186X.2014.906603
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: Camptothecin-20(s)- O -glycine ester-[ N -(3′α, 12′α-dihydroxy-24′-carbonyl-5′β-cholan)] (A2 ), 10-(3′α, 12′α-dihydroxy-5′β-cholan-24′-carboxyl)-(20 s)-camptothecin (C2 ), and 10- O -(3- O -(3′α, 12′α-dihydroxy-24′-carbonyl-5′β-cholan)-propyl)-(20 S )-camptothecin (D2 ) are novel camptothecin-deoxycholic acid analogues. MTT assays were performed to assess the anticancer activity of these compounds against hepatocellular carcinoma SMMC-7721, breast carcinoma MCF-7, and colorectal carcinoma HCT-116 cells.A2 had a high killing ability on SMMC-7721 cells selectively, butC2 andD2 did not exhibit selectivity with regard to SMMC-7721 killing. Uptake assays were performed in an effort to elucidate the transport mechanisms ofA2 into SMMC-7721 cells.A2 increased the mRNA expression of OATP1B3 (an organic anion-transporting polypeptide) and uptake ofA2 was inhibited by rifampin (inhibitor of OATP1B3), which indicated that the transporter-mediated transport ofA2 was mediated by OATP1B3. In addition, according to the western blot and apoptosis assays, we found that A2 killed SMMC-7721 cells by inducing cell apoptosis mainly via an AIF (apoptosis-inducing factor) pathway and a caspase-dependent mitochondria apoptosis pathway.