Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition
The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 24(2023), 8 vom: 11. Apr. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kang, Myung-Ji [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Diplacone |
|---|
| Anmerkungen: |
Date Completed 01.05.2023 Date Revised 09.11.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms24087057 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356117952 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356117952 | ||
| 003 | DE-627 | ||
| 005 | 20231226065801.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms24087057 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1187.xml |
| 035 | |a (DE-627)NLM356117952 | ||
| 035 | |a (NLM)37108220 | ||
| 035 | |a (PII)7057 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kang, Myung-Ji |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.05.2023 | ||
| 500 | |a Date Revised 09.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a diplacone (DP) | |
| 650 | 4 | |a ferroptosis | |
| 650 | 4 | |a mitochondria permeability transition (MPT) | |
| 650 | 4 | |a vacuolation | |
| 650 | 7 | |a diplacone |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Glutathione |2 NLM | |
| 650 | 7 | |a GAN16C9B8O |2 NLM | |
| 650 | 7 | |a Mitochondrial Permeability Transition Pore |2 NLM | |
| 700 | 1 | |a Ryu, Hyung Won |e verfasserin |4 aut | |
| 700 | 1 | |a Oh, Eun Sol |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yu Na |e verfasserin |4 aut | |
| 700 | 1 | |a Huh, Yang Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Ji-Yoon |e verfasserin |4 aut | |
| 700 | 1 | |a Oh, Seon Min |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Su-Yeon |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Yhun Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Doo-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Ro, Hyunju |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Sung-Tae |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Su Ui |e verfasserin |4 aut | |
| 700 | 1 | |a Moon, Dong-Oh |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Mun-Ock |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 24(2023), 8 vom: 11. Apr. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:8 |g day:11 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms24087057 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 8 |b 11 |c 04 | ||