Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells
Gliomas, the most prevalent primary brain tumors, exhibit a poor five-year survival rate despite advances in various treatments, necessitating further studies to understand tumor progression and develop new therapies, particularly targeting EphA2, which is implicated in vasculogenic mimicry and glio...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402500475X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585144387502080 |
|---|---|
| author | Huangde Fu Shengtian Wu Hechun Shen Kai Luo Zhongxiang Huang Nankun Lu Yaolin Li Qian Lan Yishun Xian |
| author_facet | Huangde Fu Shengtian Wu Hechun Shen Kai Luo Zhongxiang Huang Nankun Lu Yaolin Li Qian Lan Yishun Xian |
| author_sort | Huangde Fu |
| collection | DOAJ |
| description | Gliomas, the most prevalent primary brain tumors, exhibit a poor five-year survival rate despite advances in various treatments, necessitating further studies to understand tumor progression and develop new therapies, particularly targeting EphA2, which is implicated in vasculogenic mimicry and glioma progression. Dihydroartemisinin (DHA) has shown anti-glioma effects through mechanisms such as PERK-related ferroptosis and inhibition of proliferation and angiogenesis, although its interaction with EphA2 in mediating these effects requires further investigation. In this study, we revealed that DHA significantly inhibits the formation of vasculogenic-like networks, the stemness of C6 glioma stem cells and the growth of glioma by inhibiting the expression of EphA2. Mechanistic investigations indicated that PI3K/Akt pathway at least partly mediated this function, since overexpression of EphA2 reversed the anti-tumor effects of DHA. Conclusively, the current report provides evidence that DHA, PI3K/Akt/EphA2 blockage, and VM inhibition are promising therapies for glioma. |
| format | Article |
| id | doaj-art-9dec2577a5434b26b7184003dc9986a4 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-9dec2577a5434b26b7184003dc9986a42025-01-27T04:22:04ZengElsevierHeliyon2405-84402025-02-01113e42095Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cellsHuangde Fu0Shengtian Wu1Hechun Shen2Kai Luo3Zhongxiang Huang4Nankun Lu5Yaolin Li6Qian Lan7Yishun Xian8Department of Neurosurgery, The Second Nanning People's Hospital, Guangxi, China; Department of Neurosurgery, The Third Nanning People’s Hospital, Guangxi, China; Corresponding author. Department of Neurosurgery, The Second Nanning People's Hospital, Guangxi, China.Department of Neurosurgery, The Second Nanning People's Hospital, Guangxi, ChinaDepartment of Neurosurgery, The Second Nanning People's Hospital, Guangxi, ChinaDepartment of Neurosurgery, The Second Nanning People's Hospital, Guangxi, ChinaDepartment of Pathology, The Second Nanning People’s Hospital, Guangxi, ChinaDepartment of Neurosurgery, The Second Nanning People's Hospital, Guangxi, ChinaDepartment of Neurosurgery, The Second Nanning People's Hospital, Guangxi, ChinaDepartment of Clinical Laboratory, The Second Nanning People's Hospital, Guangxi, ChinaDepartment of Neurosurgery, The Second Nanning People's Hospital, Guangxi, ChinaGliomas, the most prevalent primary brain tumors, exhibit a poor five-year survival rate despite advances in various treatments, necessitating further studies to understand tumor progression and develop new therapies, particularly targeting EphA2, which is implicated in vasculogenic mimicry and glioma progression. Dihydroartemisinin (DHA) has shown anti-glioma effects through mechanisms such as PERK-related ferroptosis and inhibition of proliferation and angiogenesis, although its interaction with EphA2 in mediating these effects requires further investigation. In this study, we revealed that DHA significantly inhibits the formation of vasculogenic-like networks, the stemness of C6 glioma stem cells and the growth of glioma by inhibiting the expression of EphA2. Mechanistic investigations indicated that PI3K/Akt pathway at least partly mediated this function, since overexpression of EphA2 reversed the anti-tumor effects of DHA. Conclusively, the current report provides evidence that DHA, PI3K/Akt/EphA2 blockage, and VM inhibition are promising therapies for glioma.http://www.sciencedirect.com/science/article/pii/S240584402500475XDihydroartemisininEphA2GliomaMalignant behaviorsVasculogenic mimicry |
| spellingShingle | Huangde Fu Shengtian Wu Hechun Shen Kai Luo Zhongxiang Huang Nankun Lu Yaolin Li Qian Lan Yishun Xian Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells Heliyon Dihydroartemisinin EphA2 Glioma Malignant behaviors Vasculogenic mimicry |
| title | Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells |
| title_full | Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells |
| title_fullStr | Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells |
| title_full_unstemmed | Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells |
| title_short | Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells |
| title_sort | dihydroartemisinin inhibits epha2 pi3k akt pathway mediated malignant behaviors and vasculogenic mimicry in glioma stem cells |
| topic | Dihydroartemisinin EphA2 Glioma Malignant behaviors Vasculogenic mimicry |
| url | http://www.sciencedirect.com/science/article/pii/S240584402500475X |
| work_keys_str_mv | AT huangdefu dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT shengtianwu dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT hechunshen dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT kailuo dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT zhongxianghuang dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT nankunlu dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT yaolinli dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT qianlan dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells AT yishunxian dihydroartemisinininhibitsepha2pi3kaktpathwaymediatedmalignantbehaviorsandvasculogenicmimicryingliomastemcells |