scholarly journals Inhibition of ALDH1A1 Activity in Cisplatin-Resistant Ovarian Cancer Cells Alters Their Cancer Stemness, Cell Cycle Profile and Mitochondrial Respiration Rate

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1023-A1024
Author(s):  
Ilangovan Ramachandran ◽  
Sivakumar Ramadoss ◽  
Suvajit Sen ◽  
Selvendiran Karuppaiyah ◽  
R Ileng Kumaran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Mitochondrial Respiration ◽  
Ovarian Cancer Cells ◽  
Cancer Stemness ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Chemoresistant Ovarian Cancer

Abstract Introduction: Ovarian cancer is one of the leading cause of morbidity and death among women, with a five-year relative survival rate of only 30% in patients diagnosed with distant metastasis. The ovarian cancer cells initially respond to first-line platinum drug cisplatin [cis-diamminedichloroplatinum(II) (CDDP)] treatment. But, they subsequently develop resistance to CDDP and eventually exhibit chemoresistance. Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the key functional markers of ovarian cancer stem cells (CSCs) that confers cancer stemness and therapeutic resistance, and is associated with poor prognosis and patient survival. In this study, we have assessed the anticancer effects of the ALDH1A1 inhibitor, A37, in CDDP-resistant ovarian cancer cells in vitro. Experimental Methods: SK-OV-3-CDDP, cisplatin-resistant ovarian cancer cells were treated with different concentrations of the small molecule inhibitor of ALDH1A1, A37. We determined the cell proliferation using water-soluble tetrazolium salt (WST-1) assay at 24 and 48 h. The distribution of cell division phases by cell cycle analysis and oxygen consumption rate (OCR) via seahorse extracellular flux analysis were assessed by flow cytometry and seahorse XFe24 analyzer, respectively. Furthermore, we examined the protein expression of key signaling molecules by western blot analysis and cancer stemness by tumorsphere formation assay. Results: Treatment of SK-OV-3-CDDP cells with A37 significantly reduced the ovarian cancer cell proliferation. Interestingly, A37 induced cell cycle arrest as observed by an increase in G1 phase of the cell cycle. Additionally, A37 reduced the mitochondrial respiration of ovarian cancer cells as observed by the decrease in basal OCR. Moreover, A37 treatment markedly decreased the expression of WW domain containing transcription regulator 1 (WWTR1) protein [also called as transcriptional co-activator with PDZ-binding motif (TAZ)], which is a key downstream effector of mammalian Hippo signaling pathway that promotes cancer stemness, metastasis and chemoresistance. Importantly, A37 reduced the number and size of the tumorspheres. Conclusions: Our study suggests that inhibiting the ALDH1A1 activity using A37 reduced the cell proliferation and induced cell cycle arrest in CDPP-resistant ovarian cancer cells. The mechanism by which A37 elicits its anticancer effects on ovarian cancer cells include impairment in mitochondrial respiration that could alter cancer cell metabolism, and a decrease in WWTR1/TAZ expression and tumorsphere formation that could suppress cancer stemness. Our findings demonstrate that inhibition of ALDH1A1 could effectively eliminate the chemoresistant ovarian cancer cells, and therefore, new strategies targeting ALDH1A1 could lead to the development of novel therapeutics for aggressive chemoresistant ovarian cancer.

scholarly journals Anticancer effect of 7-hydroxycoumarin in cisplatin-resistant ovarian cancer cell is mediated via apoptosis induction, caspase activation and cell cycle arrest at G2M phase

2022 ◽  
Vol 20 (2) ◽  
pp. 281-286
Author(s):  
Hongmei Wang ◽  
Yina Wang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Anticancer Effect ◽  
Cycle Arrest

Purpose: To investigate the anticancer effects of 7-hydroxycoumarin against cisplatin-resistant ovarian cancer cell line, and the underlying mechanism(s). Methods: Cell proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The 4’,6-diamidino-2-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) dual staining methods were used for measuring cell apoptosis in terms of DNA damage. Flow cytometry was used for analysis of mitosis of cancer cells, while protein expression levels were assayed with western blotting. Results: The 7-hydroxycoumarin preferentially inhibited the proliferation of the ovarian cancer cells, but had significantly less prominent effects on normal cells (p < 0.05). The decrease in cell proliferation was due to induction of cell apoptosis via caspase-linked apoptotic pathway. Treatment with 7- hdoxycoumarin further led to the arrest of cancer cell cycle at G2/M stage (p < 0.05) via down-regulation of the expressions of regulatory proteins that promote mitotic entry. Conclusion: 7-Hydroxycoumarin exerts significant anticancer effect against cisplatin-resistant ovarian cancer cells via decrease in cell proliferation, induction of apoptosis and mitotic cell cycle arrest. Thus, the compound could emerge as a vital lead molecule in the treatment of cisplatin-resistant type of human ovarian cancer.

Abstract 4087: ALDH1A1 inhibitor induces cell cycle arrest and reduces cell proliferation of cisplatin-resistant ovarian cancer cells

2020 ◽  
Author(s):  
Ilangovan Ramachandran ◽  
Sivakumar Ramadoss ◽  
Selvendiran Karuppaiyah ◽  
Lauren Nathan ◽  
R. Ileng Kumaran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

scholarly journals Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

2010 ◽  
Vol 9 (1) ◽  
pp. 47 ◽  
Author(s):  
Christopher S Bryant ◽  
Sanjeev Kumar ◽  
Sreedhar Chamala ◽  
Jay Shah ◽  
Jagannath Pal ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

Silencing of miR-1246 Induces Cell Cycle Arrest and Apoptosis in Cisplatin-Resistant Ovarian Cancer Cells by Promoting ZNF23 Transcription

2021 ◽  
pp. 1-13
Author(s):  
Lu Cai ◽  
Qian Zhang ◽  
Lili Du ◽  
Feiyun Zheng
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Luciferase Reporter ◽  
Cycle Phase ◽  
Ovarian Cancer Cells ◽  
Tunel Staining ◽  
Cycle Arrest

Ovarian cancer (OC) is the most frequent cause of death among patients with gynecologic malignancies. In recent years, the development of cisplatin (DDP) resistance has become an important reason for the poor prognosis of OC patients. Therefore, it is vital to explore the mechanism of DDP resistance in OC. In this study, microRNA-1246 (miR-1246) expression in OC and DDP-resistant OC cells was determined by RT-qPCR, and chemosensitivity to DDP was assessed by the CCK-8 assay. A dual-luciferase reporter assay was performed to confirm the interaction between miR-1246 and zinc finger 23 (<i>ZNF23</i>), while changes in <i>ZNF23</i> expression were monitored by RT-qPCR, immunofluorescence, and western blot assays. Moreover, cell proliferation, cycle phase, and apoptosis were determined by EdU staining, flow cytometry, TUNEL staining, and Hoechst staining. Our data showed that miR-1246 was highly expressed in DDP-resistant OVCAR-3 and TOV-112D cells. Functionally, overexpression of miR-1246 markedly enhanced DDP resistance and cell proliferation, and suppressed cell cycle arrest and apoptosis of OC cells. Inhibition of miR-1246 expression significantly attenuated DDP resistance and cell proliferation, and increased cell cycle arrest and apoptosis in DDP-resistant OC cells. Furthermore, <i>ZNF23</i> was identified as a target gene of miR-1246, and ZNF23 protein expression was notably downregulated in DDP-resistant OC cells. Moreover, overexpression of miR-1246 significantly downregulated the <i>ZNF23</i> levels in OVCAR-3 and TOV-112D cells, and inhibition of miR-1246 upregulated the <i>ZNF23</i> levels in the DDP-resistant OVCAR-3 and TOV-112D cells. In conclusion, miR-1246 might be a novel regulator of DDP-resistant OC that functions by regulating <i>ZNF23</i> expression in DDP-resistant cells, as well as cell proliferation, cell cycle progression, and apoptosis.

191 RISK ASSESSMENT OF BISPHENOL A, AN ENDOCRINE DISRUPTOR, VIA PROLIFERATIVE EFFECT ON THE GROWTH OF ESTROGEN-DEPENDENT OVARIAN CANCER IN CELLULAR AND ANIMAL MODELS

2013 ◽  
Vol 25 (1) ◽  
pp. 244
Author(s):  
K.-A. Hwang ◽  
K.-C. Choi
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Bisphenol A ◽  
Cancer Cells ◽  
The Body ◽  
Brdu Incorporation ◽  
Ovarian Cancer Cells ◽  
Tumour Proliferation

One of estrogens in the body, 17β-oestradiol (E2), is a pleiotropic hormone that regulates the growth and differentiation of many tissues and also acts as a mitogen that promotes the development and proliferation of hormone-responsive cancers such as breast and ovarian carcinomas. Xenoestrogens are chemical compounds that imitate oestrogen in living organisms and are classified as a type of endocrine-disrupting chemical (EDC). Bisphenol A (BPA) is a widely used industrial compound, and also known as an EDC and especially a xenoestrogen. In this study, we examined the effect of E2 or BPA on the cell growth of BG-1 ovarian cancer cells in vivo and in vitro. In the cell proliferation assay in vitro, E2 or BPA increased the growth of the BG-1 ovarian cancer cells expressing oestrogen receptors (ER). Their proliferation activity was reversed by the treatment of ICI 182 780, a well-known antagonist of ER, which demonstrates that the cell proliferation by E2 or BPA is mediated by ER and BPA certainly acts as a xenoestrogen in the BG-1 ovarian cancer cells. Clearly, E2 and BPA increased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition. These reagents also decreased the expression of p21, a potent cyclin-dependent kinase (CDK) inhibitor that arrests the cell cycle in the G1 phase. As a result, they promoted the proliferation of BG-1 cells via upregulation of the cell cycle progression. In mice xenograft models transplanted with BG-1 ovarian cancer cells, E2 or BPA administration significantly induced the tumour proliferation compared with vehicle (corn oil) treatment for 10 weeks, which was identified by the measurement of tumour volume and histological analysis on tumour tissues such as hematoxylin and eosin (H&E) staining and BrdU incorporation assay. Taken together, as an EDC having a xenoestrogenic activity, BPA was demonstrated to have a risk of tumour proliferation in oestrogen-dependent cancers such as ovarian cancer. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of government of Korea (no. 2011-0015385).

CA 125 Production and Release by Ovarian Cancer Cells In Vitro

1998 ◽  
Vol 13 (4) ◽  
pp. 200-206 ◽  
Author(s):  
E.P. Beck ◽  
A. Moldenhauer ◽  
E. Merkle ◽  
F. Kiesewetter ◽  
W. Jäger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Tumor ◽  
Cellular Growth ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Cell Cycle Distribution ◽  
Cycle Arrest

The antigenic determinant CA 125 is a high molecular weight glycoprotein which is elevated in more than 80% of patients with epithelial ovarian cancer. Despite its good performance as a human tumor marker, only little is known about its physiological function. According to recent publications, CA 125 production and release appear to be related to cellular growth. In order to investigate this putative relationship more closely, we analyzed the pattern of CA 125 production and release by ovarian cancer cells during exponential cell growth, during cell cycle arrest by colchicine and during inhibition of cellular protein synthesis by cycloheximide. The results were correlated with the cell cycle distribution. According to our results, the main determinant of CA 125 release into the culture supernatant is the total cell count. Although cell cycle arrest in the G2 + M phase by means of colchicine treatment resulted in the death of most cells, which was reflected by an increased release of CA 125, no differences in the intracellular production rate between colchicine treated and untreated cells were seen. In contrast, treatment of cells with cycloheximide not only resulted in decreasing cell numbers but also in a complete inhibition of CA 125 production by surviving cells.

Sign in / Sign up

Export Citation Format

Share Document