Curcumin polymers as anticancer conjugates.

Abstract

Curcumin has been shown highly cytotoxic towards various cancer cell lines, but its water-insolubility and instability make its bioavailability exceedingly low and thus it generally demonstrates low anticancer activity in in vivo tests. Herein, we report a novel type of polymer-drug conjugates--the high molecular weight curcumin polymers (polycurcumins) made by condensation polymerization of curcumin. The polycurcumins as backbone-type conjugates have advantages of high drug loading efficiency, fixed drug loading contents, stabilized curcumin in their backbones, and tailored water-solubility. The polycurcumins may have many potential applications and their antitumor activities are investigated in this work. The polycurcumins are cytotoxic to cancer cells, but a polyacetal-based polycurcumin (PCurc 8) is highly cytotoxic to SKOV-3, OVCAR-3 ovarian cancers, and MCF-7 breast cancer cell lines. It can be quickly taken up by cancer cells into their lysosomes, where PCurc 8 hydrolyzes and releases active curcumin. It arrests SKOV-3 cell cycle at G(0)/G(1) phase in vitro and induces cell apoptosis partially through the caspase-3 dependent pathway. In vivo, intravenously (i.v.) injected PCurc 8 shows remarkable antitumor activity in SKOV-3 intraperitoneal (i.p.) xenograft tumor model.

• Authors: Huadong Tang, Caitlin J Murphy, Bo Zhang, Youqing Shen, Edward A Van Kirk, William J Murdoch, Maciej Radosz
• Journal: Biomaterials (Biomaterials) Vol. 31 Issue 27 Pg. 7139-49 (Sep 2010) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 20591475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Polymers
• Caspase 3
• Curcumin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, therapeutic use)
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism)
• Caspase 3 (metabolism)
• Curcumin (chemistry)
• Female
• Fluorescent Antibody Technique
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Ovarian Neoplasms (drug therapy, metabolism)
• Polymers (chemical synthesis, chemistry, therapeutic use)
• Xenograft Model Antitumor Assays