title: Andrographolide radiosensitizes human ovarian cancer SKOV3 xenografts due to an enhanced apoptosis and autophagy.
abstract: Andrographolide (AND), a diterpenoid lactone isolated from Andrographis paniculata, has been shown to have radiosensitivity in several types of cancer. Whether AND can radiosensitize ovarian cancer remains unknown. The present study investigated the radiosensitizing effects of AND in human ovarian SKOV3 xenografts and examined the molecular mechanisms of AND-mediated radiosensitization. Nude mice bearing human ovarian SKOV3 were treated with AND to investigate the effects of drug administration on tumor growth, radiosensitivity, apoptosis, and autophagy. Subsequent Western blot analysis and monodansylcadaverine (MDC) staining (autophagy analysis) were used to determine the role of AND. Finally, the pathway of apoptosis was characterized by caspase-3 activity assay as well as TUNEL analysis. AND potently sensitized SKOV3 xenografts to radiation. Moreover, apoptosis and autophagy in radiation combined with drug-treated xenografts increased significantly compared with the simple drug or single radiation treatment. This result was associated with an increase in the Bax/Bcl-2 protein ratio and p-p53 expression after exposure to combination treatment. Meanwhile, the level of Beclin 1 and Atg5 and the conversion from LC3-I to LC3-II, three important proteins involved in autophagy, were increased. AND acts as a strong radiosensitizer in human ovarian SKOV3 xenografts in vivo by increasing the Bax/Bcl-2 protein ratio and promoting the activation of caspase-3, leading to enhanced apoptosis as well as autophagy.
authors.affiliation: Radiation Oncology Department, Panyu Central Hospital, Guangzhou, China.|Cancer Institute of Panyu, Guangzhou, 510120, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. xings_qiu@126.com.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004224:Diterpenes; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; C030419:andrographolide
keywords: Andrographolide; Apoptosis; Autophagy; Ovarian cancer; Radiation