title: 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.
authors.affiliation: Division of Pharmaceutics, CSIR-Central Drug Research Institute, Chattar Manzil Palace, 1-M.G. Marg, Lucknow 226001, India.
authors.forename: Prathap Reddy
authors.initials: PR
authors.lastname: Muktapuram
authors.forename: Rishi Kumar
authors.initials: RK
authors.lastname: Gara
authors.forename: Komal
authors.initials: K
authors.lastname: Sharma
authors.forename: Chilappa
authors.initials: C
authors.lastname: Rohit
authors.forename: Kolupula
authors.initials: K
authors.lastname: Srinivas
authors.forename: Durga Prasad
authors.initials: DP
authors.lastname: Mishra
authors.forename: Surendar Reddy
authors.initials: SR
authors.lastname: Bathula
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D020868:Gene Silencing / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D034741:RNA, Small Interfering