Interaction of saffron carotenoids as anticancer compounds with ctDNA, Oligo (dG.dC)15, and Oligo (dA.dT)15.
Crocin and crocetin are two important natural saffron carotenoids, which, along with dimethylcrocetin (DMC) as a semi-synthetic product, are responsible for its color. Many biological properties of saffron have been reported, among which the anticancer property is the most important. Some anticancer drugs have direct interaction with DNA, and thus the present study attempted to investigate the interaction of three major saffron carotenoids-crocin, crocetin, and DMC--with calf thymus DNA (ctDNA) and oligonucleotides. The spectrophotometric data showed some changes in ctDNA absorption spectra due to the formation of complex with saffron extract and each of these three components. Also, all the three components caused the quenching of the fluorescence emission of ctDNA-ethidium bromide complex. The Scatchard analysis of these data indicated a noncompetitive manner for quenching, which is accompanied by the outside groove-binding pattern. The circular dichroism (CD) spectra also indicated the nonintercalative binding and induction of the conformational changes, and B to C transition in ctDNA structure and then unstacking of ctDNA bases at higher concentrations of the carotenoids. The CD spectra of G.C and A.T oligonucleotides after addition of these carotenoids indicated the transition from B- to C-DNA, which is very similar to the ctDNA spectral changes. The DeltaG(H(2)O), the best parameter for the estimation of macromolecule stability, was determined for ctDNA denaturation using dodecyl trimethylammonium bromide in the absence and presence of crocin, crocetin, or DMC. Our results showed a decrease in the Delta G(H(2)O), indicating the ctDNA destabilization due to its interaction with the mentioned ligands. In conclusion, the results show that saffron and its carotenoids interact with DNA and induce some conformational changes in it. Of these carotenoids, the order of potential of interaction with DNA is crocetin > DMC >> crocin.
Bathaie
S Zahra
SZ
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. bathai_z@modares.ac.ir
Bolhasani
Azam
A
Hoshyar
Reyhane
R
Ranjbar
Bijan
B
Sabouni
Farzaneh
F
Moosavi-Movahedi
Ali-Akbar
AA
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002338:Carotenoids / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002942:Circular Dichroism; D027622:Crocus / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D011067:Poly dA-dT / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014801:Vitamin A / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D009838:Oligodeoxyribonucleotides; C016023:oligo(dA-dT); C487773:trans-sodium crocetinate; D014801:Vitamin A; D011067:Poly dA-dT; D002338:Carotenoids; C519269:dimethylcrocetin; C052201:oligo(dG-dC); C029036:crocin; D004247:DNA