2. Academic Validation
  3. CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer

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

  • Mol Med. 2019 May 28;25(1):23. doi: 10.1186/s10020-019-0089-y.
Sungha Lee 1,  Jung Yoon Ho 2 3,  Jing Jing Liu 2 3,  Hyewon Lee 4,  Jae Young Park 2,  Minwha Baik 2,  Minji Ko 2,  Seon Ui Lee 2,  Youn Jin Choi 5 6,  Soo Young Hur 7 8
Affiliations

Affiliations

  • 1 Departments of Obstetrics and gynecology, Gangseo MizMedi, Ganseogu Gangseoro 295, Seoul, 07639, Republic of Korea.
  • 2 Department of Obstetrics and gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea.
  • 3 Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea.
  • 4 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Gangnam gu Ilwonro 81, Seoul, 06351, Republic of Korea.
  • 5 Department of Obstetrics and gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea. yunno@catholic.ac.kr.
  • 6 Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea. yunno@catholic.ac.kr.
  • 7 Department of Obstetrics and gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea. hursy@catholic.ac.kr.
  • 8 Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea. hursy@catholic.ac.kr.
PMID: 31138113 DOI: 10.1186/s10020-019-0089-y
Abstract

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.

Keywords

CKD-602; Cell cycle arrest; Cervical cancer; Invasion assay; Topoisomerase inhibitor.

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