Transfer RNA bindings to antitumor estradiol-platinum(II) hybrid and cisplatin.
The anticancer platinum (Pt) drugs exert their antitumor activity by direct or indirect Pt-DNA binding. It has been shown that Pt drugs can induce major DNA damage and minor RNA damage during cancer treatment. A recent report showed that a new anticancer estradiol-Pt(II) hybrid molecule (CD-37) binds DNA bases indirectly, while being more effective than cis-diaminedichloroplatinum(II) (cisplatin) against several types of cancer. In this report, we examine the bindings of CD-37 and cisplatin drugs with transfer RNA (tRNA) in vitro and compare the results to those of the corresponding Pt-DNA complexes. Solutions containing various CD-37 or cisplatin concentrations were reacted with tRNA at physiological pH. Using Fourier transform infrared (FTIR), UV-visible, and circular dichroism spectroscopic methods, the drug binding mode, the binding constant, and RNA structural variations are determined for Pt-tRNA complexes in aqueous solution. Structural analysis showed direct binding of cisplatin drug to guanine and adenine N7 sites, while both direct and indirect interactions of CD-37 with tRNA bases and the backbone phosphate group were observed. The overall binding constants estimated were K(CD-37) = 2.77 (+/-0.90) x 10(4) M(1) and K(cisplatin) = 1.72 (+/-0.50) x 10(4) M(1). Major aggregation of tRNA occurs at high CD-37 concentrations, while RNA remains in the A-family structure.
N'soukpoé-Kossi
Christophe N
CN
Groupe de Recherche en Biologie Végétale, Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
Descôteaux
Caroline
C
Asselin
Eric
E
Bariyanga
Joseph
J
Tajmir-Riahi
Heidar-Ali
HA
Bérubé
Gervais
G
D000970:Antineoplastic Agents / Q000378:metabolism*; D001665:Binding Sites; D002942:Circular Dichroism; D002945:Cisplatin / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009944:Organoplatinum Compounds / Q000378:metabolism*; D012331:RNA, Fungal / Q000737:chemistry / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
C487473:17beta-estradiol platinum(II); D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012331:RNA, Fungal; D004958:Estradiol; D012343:RNA, Transfer; D002945:Cisplatin