 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 23, 2024 |
| Title |
Daphnetin induces ferroptosis in ovarian cancer by inhibiting NAD(P)H: Quinone oxidoreductase 1 (NQO1) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Ferroptosis, an emerging nonapoptotic, regulated cell death process distinguished by iron accumulation and subsequent lipid peroxidation, is intricately implicated in the development and progression of multiple cancer types. Here, we aimed to reveal that triggering ferroptosis is a promising treatment strategy for ovarian cancer. In this study, we not only validated that daphnetin caused ferroptosis, but evaluated the effects of daphnetin (and/or cisplatin) in vitro and vivo.Here, we elucidated that daphnetin, a natural product isolated from Daphne Korean Nakai, can exert antitumor effects by inducing the death and suppressing the migration of ovarian cancer cells. Subsequently, transcriptome analysis and ferroptosis inhibitor (Fer-1 and DFO) experiments revealed that there is a close correlation between daphnetin and ferroptosis in ovarian cancer. We further found that daphnetin induced ferroptosis in ovarian cancer cells, as evidenced by the accumulation of intracellular ferrous iron (Fe2+), reactive oxygen species (ROS) and lipid peroxides, as well as the depletion of glutathione (GSH) and ferroptosis indicators (SLC7A11 and GPX4). In particular, daphnetin effectively reduced the mRNA and protein levels of NQO1 (a ubiquitous flavoenzyme), and a high expression level of NQO1 was significantly associated with poor prognosis and ferroptosis resistance in ovarian cancer patients. Furthermore, NQO1 activation markedly attenuated daphnetin-induced cell death, migration and ferroptotic events in vitro and vivo. Interestingly, we also found that treatment with daphnetin, a negative regulator of NQO1, in combination with cisplatin synergistically induced ovarian cancer cell cytotoxicity. This study demonstrated that daphnetin induces ferroptosis by inhibiting NQO1 in ovarian cancer cells. Our findings identified NQO1 as a new daphnetin target and suggested that targeting NQO1 might have therapeutic effects on ovarian cancer.
|
| |
|
| Overall design |
To illustrate the specific mechanism that daphnetin can induce cell death and hinder the cell invasion and migration of ovarian cancer, RNA sequencing was conducted to identify the differentially expressed mRNAs between control-treated and daphnetin-treated A2780 (or SKOV3) cells, thereby identifying the closely related signaling pathways and targets.
|
| |
|
| Contributor(s) |
Ma N, Zhang M, Wei Z, Zhang S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 18, 2024 |
| Last update date |
May 23, 2024 |
| Contact name |
Ning Ma |
| E-mail(s) |
maning22@mails.jlu.edu.cn
|
| Phone |
15844021269
|
| Organization name |
The First Hospital of Jilin University
|
| Street address |
Xinmin Road 71, The First Hospital of Jilin University
|
| City |
Chang chun |
| ZIP/Postal code |
130001 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (18)
|
| GSM8279181 |
A2780 cells, Daphnetin(20mg/L) 1 |
| GSM8279182 |
A2780 cells, Daphnetin(20mg/L) 2 |
| GSM8279183 |
A2780 cells, Daphnetin(20mg/L) 3 |
| GSM8279184 |
A2780 cells, Daphnetin(40mg/L) 1 |
| GSM8279185 |
A2780 cells, Daphnetin(40mg/L) 2 |
| GSM8279186 |
A2780 cells, Daphnetin(40mg/L) 3 |
| GSM8279187 |
SKOV3 cells, DMSO 1 |
| GSM8279188 |
SKOV3 cells, DMSO 2 |
| GSM8279189 |
SKOV3 cells, DMSO 3 |
| GSM8279190 |
SKOV3 cells, Daphnetin(20mg/L) 1 |
| GSM8279191 |
SKOV3 cells, Daphnetin(20mg/L) 2 |
| GSM8279192 |
SKOV3 cells, Daphnetin(20mg/L) 3 |
| GSM8279193 |
SKOV3 cells, Daphnetin(40mg/L) 1 |
| GSM8279194 |
SKOV3 cells, Daphnetin(40mg/L) 2 |
| GSM8279195 |
SKOV3 cells, Daphnetin(40mg/L) 3 |
|
| Relations |
| BioProject |
PRJNA1113162 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267812_All_reads_counts.xls.gz |
5.4 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...