Compacting effect of BBR3464, a new-generation trisplatinum anticancer agent, on DNA.
BBR3464 is a trinuclear platinum compound of formula [{trans-PtCl(NH(3))(2)}(2)-mu-trans-Pt(NH(3))(2){NH(2)(CH(2))(6)NH(2)}(2)](4+). It is a new-generation platinum chemotherapeutic agent that exhibits cytotoxicity at ten to thousand times lower dose limit compared to the well-known platinum drug cisplatin, in cisplatin-sensitive as well as in cisplatin-resistant cells. DNA is thought to be the primary cellular target of BBR3464. In this work, we have applied high-resolution atomic force microscopy (AFM) for the first time, to obtain direct information on BBR3464-induced structural changes of DNA. It is found that the DNA molecules get compacted after treatment with BBR3464, for the drug:DNA molar ratio and the drug treatment period of 0.01 and 48 h, respectively. These values of molar ratio and incubation period have been obtained previously, as a result of biochemical optimization studies carried out for achieving maximum drug effects. The DNA structural changes, as observed in AFM topographs, have been correlated to the bulk level spectroscopic information. A remark on the significance of BBR3464-induced DNA compaction with respect to the available AFM reports on DNA modification by cisplatin has been made.
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India.
T
T
Banerjee
P
P
Dubey
R
R
Mukhopadhyay
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D004247:DNA; C114062:BBR 3464