Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage¶

Abstract

Photosensitized DNA damage participates in solar-UV carcinogenesis, photogenotoxicity and phototoxicity. A chemoprevention of photosensitized DNA damage is one of the most important methods for the above phototoxic effects. In this study, the chemopreventive action of xanthone (XAN) derivatives (bellidifolin [BEL], gentiacaulein [GEN], norswertianin [NOR] and swerchirin [SWE]) on DNA damage photosensitized by riboflavin was demonstrated using [32P]-5'-end-labeled DNA fragments obtained from genes relevant to human cancer. GEN and NOR effectively inhibited the formation of piperidine-labile products at consecutive G residues by photoexcited riboflavin, whereas BEL and SWE did not show significant inhibition of DNA damage. The four XAN derivatives decrease the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidative product of G, by photoexcited riboflavin. The preventive action for the 8-oxodGuo formation of these XAN derivatives increased in the following order: GEN>NOR>>BEL>SWE. A fluorescence spectroscopic study and ab initio molecular orbital calculations suggested that the prevention of DNA photodamage is because of the quenching of the triplet excited state of riboflavin by XAN derivatives through electron transfer. This chemoprevention is based on neither antioxidation nor a physical sunscreen effect; rather, it is based on the quenching of a photosensitizer. In conclusion, XAN derivatives, especially GEN, may act as novel chemopreventive agents by the quenching mechanism of an excited photosensitizer.

Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

“…Skin cancer and melanoma α-mangostin (2) Inhibited in vitro cell proliferation, adhesion and invasion of SK-MEL-28, B16-F10 and A375 cells Wang et al (2011), Beninati et al (2014) Inhibited tumor incidence and hyperplasia in DMBA-TPA-induced mice Wang et al 2017 13Inhibited skin carcinogenesis in SKH-1 hairless mice exposed to solar UV Li et al (2012) Induced cell cycle arrest at G2/M phase by increasing cyclin B1 and phosphorylated Cdk 1 Inhibited activation of MAPK and NF-κB cascades by competitively inhibiting ERK2 kinases Gentiacaulein (15) Chemoprevention by photoprotection and quenching of excited riboflavin Hirakawa et al (2005) Norswertianin (16) Chemoprevention by photoprotection and quenching of excited riboflavin Hirakawa et al (2005) (Continued on following page) production of nerve growth factors (NGF) and nerve extension that relieved the itching. Histamines, also known as imidazolethylamine, play an important role in cutaneous inflammation and contribute to the characteristic redness, wheal, flare and pruritis of AD (Buddenkotte et al, 2010).…”

“…Therefore, 4 was suggested to be effective photoprotective agents with potential applications as sunscreens, cosmetics or skin care products to protect against UVB-induced oxidative stress and the resulting skin inflammation (Petrova et al, 2011;Magcwebeba et al, 2016b). Interestingly, two other xanthone derivatives gentiacaulein (15) and norswertianin (16) were identified to be chemopreventive agents that utilized a novel quenching mechanism instead of antioxidation or physical sunscreen effects (Hirakawa et al, 2005). Using fluorescence spectroscopic techniques and ab initio molecular orbital calculations, the DNA photoprotective effects of these xanthones were found to involve the quenching of the triplet photoexcited state of riboflavin (Hirakawa et al, 2005).…”

“…Interestingly, two other xanthone derivatives gentiacaulein (15) and norswertianin (16) were identified to be chemopreventive agents that utilized a novel quenching mechanism instead of antioxidation or physical sunscreen effects (Hirakawa et al, 2005). Using fluorescence spectroscopic techniques and ab initio molecular orbital calculations, the DNA photoprotective effects of these xanthones were found to involve the quenching of the triplet photoexcited state of riboflavin (Hirakawa et al, 2005).…”

Medicinal importance of Swertia chirayita in Unani system of medicine

“…A medicinally foremost xanthone, obtained from several plants of family Gentianaceae including Swertia chirayita; having antimalarial, hypoglycemic, hepatoprotective, proheamatopoitic and weak chemo preventive pharmacological effects (Hirkawa et al, 1987) [8] .…”

Xanthones Production in Gentiana dinarica Beck Hairy Root Cultures Grown in Simple Bioreactors

“…Bioproduction of xanthones is of particular interest since they exhibited a number of very important bioactivities that could be exploited in biomedicine [10]. Thus, norswertianin was shown to display the wide spectrum of bioactivities with antibacterial, antifungal, antioxidative and hypoglycemic effects [11], as well as potential to act as a chemopreventive agent [12]. Recently, anticancerogenic activity of the crude extracts of G. dinarica hairy roots and purified norswertianin was also revealed [13].…”