title: Bisnaphthalimidopropyl spermidine induces apoptosis within colon carcinoma cells.
abstract: Bisnaphthalimido compounds bisintercalate to DNA via the major groove and are potentially potent cancer therapeutics. We incorporated natural polyamines as linkers connecting the two-naphthalimido ring moieties to create a series of novel soluble cytotoxic bisnaphthalimidopropyl polyamines (BNIPPs). Here, we determined the cytotoxicity of bisnaphthalimidopropyl spermidine (BNIPSpd) towards Caco-2 and HT-29 colon adenocarcinoma cells revealing an IC(50) value of 0.15 and 1.64 microM after 48h exposure within Caco-2 and HT-29 cells, respectively. After 4h, >/=0.5 microM BNIPSpd treatment-induced significant DNA damage. After 24h exposure a concentration-dependent increase in active caspase-3 expression, chromatin condensation and internucleosomal DNA fragmentation identified apoptosis as the principal manifestation for the cytotoxicity within both cell lines. By 24h exposure, there was also a significant decline in cellular spermine and spermidine levels. It is concluded that bisnaphthalimidopropyl spermidine (BNIPSpd) toxicity primarily results from apoptosis and that BNISpd has potential to be further developed as an anti-tumour agent.
authors.affiliation: School of Pharmacy and Life Sciences, The Robert Gordon University, St. Andrew Street, Aberdeen AB25 1HG, UK.
authors.forename: Lynda D
authors.initials: LD
authors.lastname: Ralton
authors.forename: Charles S
authors.initials: CS
authors.lastname: Bestwick
authors.forename: Lesley
authors.initials: L
authors.lastname: Milne
authors.forename: Susan
authors.initials: S
authors.lastname: Duthie
authors.forename: Paul
authors.initials: P
authors.lastname: Kong Thoo Lin
mesh_terms: D000165:Acridine Orange; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000473:pathology*; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D004996:Ethidium; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011073:Polyamines; D015363:Quinolones; C439296:bisnaphthalimidopropylspermidine; D004996:Ethidium; D000165:Acridine Orange; D013095:Spermidine