CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer

التفاصيل البيبلوغرافية
العنوان: CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer
المؤلفون: Youn Jin Choi, Minji Ko, Sung Ha Lee, Minwha Baik, Seon Ui Lee, Jung Yoon Ho, Hyewon Lee, Soo Young Hur, Jing Jing Liu, Jae Young Park
المصدر: Molecular Medicine
Molecular Medicine, Vol 25, Iss 1, Pp 1-8 (2019)
بيانات النشر: Springer Science and Business Media LLC, 2019.
سنة النشر: 2019
مصطلحات موضوعية: 0301 basic medicine, Cell cycle checkpoint, Uterine Cervical Neoplasms, Apoptosis, HeLa, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Medicine, lcsh:QD415-436, Fluorescein isothiocyanate, Genetics (clinical), Cervical cancer, Mice, Inbred BALB C, biology, Flow Cytometry, G2 Phase Cell Cycle Checkpoints, 030220 oncology & carcinogenesis, Molecular Medicine, Female, CKD-602, Topoisomerase inhibitor, Research Article, medicine.drug_class, Mice, Nude, lcsh:Biochemistry, Cell cycle arrest, 03 medical and health sciences, In vivo, Cell Line, Tumor, Genetics, Animals, Humans, Propidium iodide, Molecular Biology, business.industry, lcsh:RM1-950, Invasion assay, Cell Cycle Checkpoints, medicine.disease, biology.organism_classification, Xenograft Model Antitumor Assays, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, chemistry, Cancer research, Camptothecin, Topoisomerase I Inhibitors, business, HeLa Cells
الوصف: Background Cervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated. Methods Three established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo. Results Treatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602. Conclusions This is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies. Electronic supplementary material The online version of this article (10.1186/s10020-019-0089-y) contains supplementary material, which is available to authorized users.
تدمد: 1528-3658
1076-1551
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b9e9b641da61a9a65cb84fb04a75f1c
https://doi.org/10.1186/s10020-019-0089-y
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....9b9e9b641da61a9a65cb84fb04a75f1c
قاعدة البيانات: OpenAIRE