title: Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice.
abstract: Bleomycin (BLM) is an effective anti-carcinogen. With the main detrimental effects of inducing pulmonary fibrosis on patients, its clinical use is limited. Developing agents that enhance the efficacy and attenuate the side effects of cancer chemotherapy are critical. Andrographolide (Andro), an active diterpenoid labdane component extracted from Andrographis panicula, is generally prescribed for treatment of inflammatory associated diseases. The study showed that BLM combined with Andro was significantly more effective than BLM alone on inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, promoting the capase-3 and capase-8 activity to induce cancer cell apoptosis. The underlying mechanisms may be related to the transcriptional regulation of P53/P21/Cyclin pathways. Moreover, BLM induced pulmonary fibrosis in tumor-bearing mice, but BLM combined with Andro dramatically alleviated the lesion in pulmonary fibrosis by activating the SOD, suppressing MDA and HYP production, in the meanwhile attenuating the IL-1β, TNF- α, IL-6 and TGF-β1 level. These mechanisms were associated with its effect on inhibition of protein expression of TGF-β, α-SMA, p-Smad2/3, enhanced expression of Smad7. Thus, it demonstrated that Andro might be a potential adjuvant therapeutic agent for BLM.
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhenbiao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zuqing
authors.initials: Z
authors.lastname: Su
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Chaoyue
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China; Department of Chinese Materia Medica, Guangdong Xinxing Junior College of the Traditional Chinese Medicine, Xinxing, Guangdong, People's Republic of China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Lai
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ziren
authors.initials: Z
authors.lastname: Su
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China. Electronic address: liyucui@gzucm.edu.cn.
authors.forename: Yucui
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China. Electronic address: zyx@gzucm.edu.cn.
authors.forename: Janis Yaxian
authors.initials: JY
authors.lastname: Zhan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001202:Ascitic Fluid / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D016207:Cytokines; D004224:Diterpenes; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin; C030419:andrographolide
keywords: Andrographolide; Anticancer; Bleomycin; Combination; Pulmonary fibrosis