title: Effect-enhancing and toxicity-reducing activity of usnic acid in ascitic tumor-bearing mice treated with bleomycin.
abstract: Usnic acid (UA) can be found in certain lichen species. Growing evidence suggests that UA possesses antitumoral, antioxidative and anti-inflammatory activities. Bleomycin (BLM) is widely used in the treatment of malignant ascites, however, it unexpectedly causes pulmonary fibrosis (PF). Researches show that excessive inflammatory response and oxidative stress in lung tissue is conspicuous causes of BLM-induced PF. Here we investigated mechanism underlying the effect-enhancing and toxicity-reducing activity of UA on H22-bearing mice treated with BLM. UA combined with BLM was significantly more effective than BLM alone in inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, and promoting the cleaved caspase-3 and cleaved caspase-8 activities to induce cancer cellular apoptosis. The mechanism may be associated with the transcriptional regulation of p53/p21/Cyclin pathway. Furthermore, UA effectively moderated the histopathological changes, reduced the content of MDA, HYP, TNF-α, IL-1β, IL-6 and TGF-β1, and increased the level of SOD when combined with BLM in lung tissues of H22-bearing mice, which was believed to be related to the inhibition on the protein level of p-Smad2/3 and enhancement of Smad7 expression. These findings suggested that UA might be a potential effect-enhancing and toxicity-reducing candidate for BLM in the treatment of malignant ascites.
authors.affiliation: Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
authors.forename: Zu-Qing
authors.initials: ZQ
authors.lastname: Su
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinals Development and Research, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Guo
authors.affiliation: Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
authors.forename: Chao-Yue
authors.initials: CY
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Xie
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinals Development and Research, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Yu-Cui
authors.initials: YC
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinals Development and Research, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, China.
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinals Development and Research, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinals Development and Research, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, China. Electronic address: suziren@gzucm.edu.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
authors.affiliation: Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Postdoctoral Programme, Guangzhou University of Chinese Medicine, Guangzhou 510120, China. Electronic address: hemin066@126.com.
authors.forename: Hai-Ming
authors.initials: HM
authors.lastname: Chen
mesh_terms: D000277:Adjuvants, Pharmaceutic; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001201:Ascites / Q000150:complications / Q000188:drug therapy*; D001572:Benzofurans / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D006801:Humans; D008011:Lichens / Q000276:immunology; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000517:prevention & control*; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D001572:Benzofurans; D051785:Smad Proteins; C073339:usnic acid; D001761:Bleomycin
keywords: Anticancer; Bleomycin; Combination; Pulmonary fibrosis; Usnic acid