Lichen Acids May Be Used as A Potential Drug For Cancer Therapy; by Inhibiting Mitochondrial Thioredoxin Reductase Purified From Rat Lung.
BACKGROUND
Thioredoxin reductase (E.C 1.6.4.5.; TrxR) is a widely distributed flavoprotein that catalyzes the NADPH-dependent reduction of thioredoxin (Trx) in many cellular events such as DNA synthesis, DNA repair, angiogenesis, antioxidative defense, and regulating apoptosis. Although TrxR is indispensible in protecting cells against oxidative stress, the overexpression of TrxR is seen in many aggressive tumors. Therefore, targeted inhibition of TrxR has been accepted as a new approach for chemotherapy.


OBJECTIVE
In this study, in vitro inhibition effect of the lichen acids (diffractaic, evernic, lobaric, lecanoric, and vulpinic acid) on mitochondrial TrxR purified from rat lung was investigated.


METHOD
It was the first time the enzyme was purified from rat lungs by using 2', 5'-ADP Sepharose 4B affinity chromatography. The purity of the enzyme was checked with SDS-PAGE. In vitro inhibition effect of the lichen acids was investigated spectrophotometrically. To emphasize the importance of the obtained data, the commercial anticancer drugs cisplatin and doxorubicin were used as positive controls.


RESULTS
Molecular mass of the enzyme was calculated as approximately 52.4 kDa. The enzyme was purified with a 63.6% yield, 208.3 fold, and 0.5 EU/mg proteins specific activity. The IC50 values of five lichen acids were significantly lower than IC50 values of anticancer drugs.


CONCLUSION
All of the lichen acids, especially lecanoric and vulpinic acid, exhibited much stronger inhibitory effect on TrxR than the anticancer drugs cisplatin and doxorubicin. These lichen acids have pharmacological potential as effective natural antioxidants, antimicrobials, and anticancer agents.
['Ozgencli|Ilknur|I|', 'Budak|Harun|H|', 'Ciftci|Mehmet|M|', 'Anar|Mustafa|M|']
D000818:Animals D000840:Anisoles D000970:Antineoplastic Agents D002945:Cisplatin D053630:Depsides D004305:Dose-Response Relationship, Drug D004317:Doxorubicin D004791:Enzyme Inhibitors D005663:Furans D062385:Hydroxybenzoates D007783:Lactones D008011:Lichens D008168:Lung D008297:Male D008928:Mitochondria D015394:Molecular Structure D010648:Phenylacetates D051381:Rats D017207:Rats, Sprague-Dawley D012459:Salicylates D013329:Structure-Activity Relationship D013880:Thioredoxin-Disulfide Reductase
lichen acid cancer inhibition Thioredoxin reductase mitochondrial TrxR.f rat lung.