Interaction of Saffron Carotenoids as Anticancer Compounds with ctDNA, Oligo (dG.dC)₁₅, and Oligo (dA.dT)₁₅

Abstract

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.

Platinum(II)/palladium(II) complexes with n-propyldithiocarbamate and 2,2′-bipyridine: synthesis, characterization, biological activity and interaction with calf thymus DNA

“…However, the values of G 0 (H 2 O) decreases as the temperature rises. This is as expected, because, in general, the decrease in G 0 (H 2 O) value is the main reason for the decrease in DNA stability [20]. Molar enthalpy of CT-DNA denaturation in the absence of Pt(II) and Pd(II) complexes H 0 (H 2 O) is an another important thermodynamic parameter.…”

“…This value (154 µM) is much higher as compared with the Cc 50 values of the above complexes [18]. [19][20][21], that is, both complexes (in particular Pd(II) complex) can denature DNA at low concentrations. Thus, if these complexes are used as anti-tumor agents, low doses will be needed, so this may have fewer side effects.…”

Protective Effect of Crocus sativus Stigma Extract and Crocin (trans-crocin 4) on Methyl Methanesulfonate–Induced DNA Damage in Mice Organs

“…A direct interaction with nucleic acids such as DNA and thereby protecting them from harmful damages were reported for crocin, crocetin, dimethylcrocin, and safranal, in vitro (Bathaie et al, 2007;Kanakis et al, 2007bKanakis et al, , 2007c. It could be postulated that saffron decreases DNA damage by protecting DNA nucleophilic sites.…”

DNA-Binding and Thermodynamic Parameters, Structure and Cytotoxicity of Newly Designed Platinum(II) and Palladium(II) Anti-Tumor Complexes

“…This is as expected because in general, the decrease in value is the main reason for the decrease in DNA stability. 42 The values of m for the [Pt(bpy)(Hex-dtc)]NO 3 complex are much higher than those of [Pd(bpy)(Hex-dtc)]NO 3 complex. This indicate the higher ability of Pt(II) complex to decreased the stability of CT-DNA.…”