Curcumin polymers as anticancer conjugates.
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.
Tang
Huadong
H
Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, WY 82071, USA.
Murphy
Caitlin J
CJ
Zhang
Bo
B
Shen
Youqing
Y
Van Kirk
Edward A
EA
Murdoch
William J
WJ
Radosz
Maciej
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003474:Curcumin / Q000737:chemistry*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011108:Polymers; D053148:Caspase 3; D003474:Curcumin