Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
The impact of active metabolites obtained from saffron on H1- Oligonucleotide interaction
In the recent years, the anti-tumor activity of saffron components, monoterpene aldehydes (safranal and picrocrocin) and carotenoids (crocins and crocetin) was reported by us and other research groups around the world. The molecular mechanisms of action of saffron and its constituents have been not known clearly, yet.
The transcriptional activation of genes occurs due to the histone H1 dissociation from linker DNA. Therefore H1-DNA complex has been considered as a model of chromatin. Our previous study on H1–DNA interaction in the presence of SDS (which was bound to H1 electrostatically and covered all positive charges on H1 surface) has shown the more folded structure of H1 and thus complete dissociation from DNA. We have also showed previously that some modification on histone H1 such as acetylation by aspirin, or some changes in the environment (for example in the presence of chemical chaperones like polyamines) can affect this complex and dissociate it with various degrees. In the present study, the effect of saffron active metabolites, both carotenoids and monoterpene aldehydes, on the histone H1-DNA interaction, using a specific oligonucleotide with higher affinity for histone H1 than high molecular weight DNA, is evaluated. Different techniques including gel retardation electrophoresis and circular dichroism (CD) was used. The results of gel retardation assay and CD spectra of Hl-Oligonucleotide complex showed the decrease in the complex formation in the following order crocin> picrocrocin>> safranal> crocetin. These observations in the in vitro condition led to suggesting a mechanism in which the H1 depletion may affect transcription of some genes for example tumor suppressing genes in vivo. In conclusion, saffron various applications as an anti-oxidant, anti-genotoxic, and anti-cancer agent are due to its secondary metabolites (safranal, picrocrocin, crocins and crocetin), can decrease interaction of histone H1 with DNA and reduce the H1-DNA complex formation.
Department of Clinical Biochemistry