142 - Antitumor effect of synthetic phenolic antioxidant TS-13 in Lewis lung carcinoma mouse model

Abstract

Reactive oxygen and nitrogen species are important intracellular messengers that are strongly implicated in tumor processes, yet their precise role in cancerogenesis is still largely unclear and often debatable. Plant and synthetic phenols and polyphenols are known to have antitumor effect through multiple mechanisms most importantly the one that activates Keap1/Nrf2/ARE pathway. We have previously demonstrated that water-soluble synthetic phenolic antioxidant sodium 3-(3′-tert-butyl-4′-hydroxyphenyl) propyl thiosulfonate (TS-13) increased cell susceptibility to doxorubicin in cell culture. Antitumor action of TS-13 was attributed to its effect on mitochondria followed by Keap1/Nrf2/ARE activation and subsequent autophagy and apoptosis. The effect of TS-13 on tumor growth and the oncolytic effect of doxorubicin was studied in experimental model of transplantable tumor (Lewis lung carcinoma, LLC) in mice. On day 21 after inoculation of LLC cells, tumor growth was inhibited by 32.3% in mice that received TS-13 with drinking water (100 mg/kg). Two intraperitoneal injections of doxorubicin in a cumulative dose of 8 mg/kg body weight reduced tumor growth by 49.5%, while co-administration of TS-13 and doxorubicin resulted in tumor growth inhibition by 55.4%. Animals with inoculated tumor (+ or - doxorubicin) had significantly higher rate (by 27 and 39%, respectively, p