title: Sensitization of ionizing radiation-induced apoptosis by ursolic acid.
abstract: Radiation therapy has been widely used for treating human cancers. However, cancer cells develop radioresistant phenotypes that decrease the efficacy of radiotherapy. Ionizing radiation (IR) induces the production of reactive oxygen species, which play an important role in apoptotic cell death. Therefore, radiation therapy combined with a sensitizer, which modulates cellular redox status, has the potential to enhance therapeutic efficacy in a variety of human cancers. Here, we investigated the radiosensitizing effects of ursolic acid (UA), a pentacyclic triterpenoid found in rosemary and holy basil. IR-induced apoptosis in cancer cell lines such as DU145, CT26 and B16F10 was significantly enhanced by UA, as reflected by DNA fragmentation, cellular redox status, mitochondrial dysfunction and modulation of apoptotic marker proteins. Additionally, UA combined with IR was also effective for inhibiting tumorigenesis in B16F10 melanoma cells implanted into mice. Taken together, these results suggest that applying UA together with IR may be an effective combination modality for treating cancer.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Koh
authors.forename: Jean Kyoung
authors.initials: JK
authors.lastname: Tak
authors.forename: Seon Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Woo Suk
authors.initials: WS
authors.lastname: Nam
authors.forename: Sung Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D003110:Colonic Neoplasms / Q000473:pathology; D003131:Combined Modality Therapy; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D014315:Triterpenes; D000097245:Ursolic Acid