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.
Banerjee
T
T
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India.
Dubey
P
P
Mukhopadhyay
R
R
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