Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1.
10.1007/s11655-022-3469-z
- Author:
Xue-Li WANG
1
;
Xiao-Zheng CAO
2
;
Dao-Yuan WANG
3
;
Ye-Bei QIU
3
;
Kai-Yu DENG
1
;
Jian-Guo CAO
3
;
Shao-Qiang LIN
2
;
Yong XU
4
;
Kai-Qun REN
5
Author Information
1. Medical College, Hunan University of Medicine, Huaihua, Hunan Province, 418000, China.
2. Clinical Department of Guangdong Metabolic Disease Research Centre of Integrated Chinese and Western Medicine, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510062, China.
3. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha, 410013, China.
4. Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
5. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha, 410013, China. kaiqunren@126.com.
- Publication Type:Journal Article
- Keywords:
DNA methyltransferase 1;
cancer stem cell;
casticin;
cervical cancer;
therapeutic action
- MeSH:
Female;
Humans;
Cell Line, Tumor;
HeLa Cells;
Neoplastic Stem Cells/metabolism*;
RNA, Small Interfering/metabolism*;
Uterine Cervical Neoplasms/metabolism*
- From:
Chinese journal of integrative medicine
2023;29(3):224-232
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.
METHODS:Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).
RESULTS:DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.
CONCLUSION:CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
