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Anticancer siRNA delivery by new anticancer molecule: a novel combination strategy for cancer cell killing.

Abstract
The present report describes development of a novel, bifunctional molecule possessing both selective antiproliferative activity and siRNA transfection ability. We synthesized a series of cationic lipo-benzamides and screened for in vitro anticancer activities against a panel of cancer and non-cancer cells. The molecule with a ten carbon chain-length (C10M) significantly inhibited proliferation of cancer cells via arresting the cell cycle predominantly in the G1 phase; but did not affect non-cancerous cells. C10M effectively mediated siRNA delivery in vitro. The combined anticancer effect of the delivery of C10M together with its survivin-targeting siRNA cargo was significantly (p < 0.05) superior to that of agent alone. To our knowledge, this is the first report of a dual-purpose molecule with intrinsic anticancer activity and suitability for use in siRNA delivery.
AuthorsPrathap Reddy Muktapuram, Rishi Kumar Gara, Komal Sharma, Chilappa Rohit, Kolupula Srinivas, Durga Prasad Mishra, Surendar Reddy Bathula
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 56 Pg. 400-8 (Oct 2012) ISSN: 1768-3254 [Electronic] France
PMID22926227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Benzamides
  • RNA, Small Interfering
Topics
  • Animals
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Apoptosis (drug effects)
  • Benzamides (chemical synthesis, chemistry, pharmacology)
  • COS Cells
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Drug Screening Assays, Antitumor
  • Gene Silencing (drug effects)
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Mice
  • Models, Molecular
  • Molecular Structure
  • NIH 3T3 Cells
  • RNA, Small Interfering (genetics, metabolism, pharmacology)
  • Structure-Activity Relationship

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