Anti-proliferative effects of unmodified antisense oligodeoxynucleotides targeted against c-raf mRNA: use of poly (lysine/serine) copolymers or cationic lipopolyamines.

Abstract

1. It is now known that nuclease-resistant phosphorothioate antisense oligodeoxynucleotides (ODN) have some actions that are unrelated to antisense mechanisms. In the present study we assessed the anti-proliferative effects of phosphorothioate (PS) and phosphodiester (PO; unmodified) antisense ODN targeted against c-raf mRNA on pancreatic cancer cells in vitro, using poly (lysine/serine) copolymers conjugated with polyethylene glycol (PLSP) or cationic lipopolyamines (Transfectam) as carriers. 2. The anti-proliferative effect of the PO antisense ODN was significantly (P < 0.05) greater than that of the PS ODN, either complexed with PLSP (2 mumol/L ODN) or the Transfectam (0.5 mumol/L ODN). However, the effect of the PS or PO antisense ODN was not dependent on the antisense sequence. The c-raf mRNA levels, assessed by reverse transcription-polymerase chain reaction, were obviously reduced by both PO and PS antisense ODN compared with mismatched ODN when complexed with the Transfectam (1 mumol/L ODN). 3. Although the anti-proliferative effects were mainly unrelated to antisense mechanisms, unmodified antisense ODN complexed with some carriers could be used as anti-tumour agents considering that synthetic carriers can be modified to improve functions, such as delivery.

• Authors: Y Aoki, S Kawa, Y Karasawa, A Horiuchi, K Kiyosawa
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 25 Issue 9 Pg. 702-5 (Sep 1998) ISSN: 0305-1870 [Print] Australia
• PMID: 9750959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cations
• Drug Carriers
• Oligonucleotides, Antisense
• Peptides
• Pharmaceutic Aids
• Polyamines
• RNA, Messenger
• Thionucleotides
• dioctadecylamidoglycylspermine
• Polylysine
• polyserine
• Spermine
• Polyethylene Glycols
• Proto-Oncogene Proteins c-raf
• Glycine

Topics

• Cations
• Cell Division (drug effects)
• Drug Carriers
• Glycine (administration & dosage, analogs & derivatives)
• Humans
• Oligonucleotides, Antisense (administration & dosage, pharmacology)
• Pancreatic Neoplasms (drug therapy, pathology)
• Peptides (administration & dosage)
• Pharmaceutic Aids (pharmacology)
• Polyamines (administration & dosage)
• Polyethylene Glycols (administration & dosage)
• Polylysine (administration & dosage)
• Proto-Oncogene Proteins c-raf (genetics)
• RNA, Messenger (metabolism)
• Spermine (administration & dosage, analogs & derivatives)
• Thionucleotides (administration & dosage, pharmacology)
• Tumor Cells, Cultured