Casticin induces apoptosis and cytoprotective autophagy while inhibiting stemness involving Akt/mTOR and JAK2/STAT3 pathways in glioblastoma

Yang, Xun1,2,3; Liu, Zeyuan4; Xu, Xu1,2; He, Meng1,2; Xiong, Hongtao5,6; Liu, Lijun1,2

2023-10-01

10.1002/ptr.8048

PHYTOTHERAPY RESEARCH   Impact Factor & Quartile

0951-418X

1099-1573

Glioblastoma (GBM) is the most common malignant glioma. However, the current systemic drugs cannot completely cure GBM. Casticin is a methoxylated flavonol compound isolated from a traditional Chinese medicine Vitex rotundifolia L.f. and exhibits a strong antitumor activity in multiple human malignancies. This study was aimed to explore the effects and underlying mechanisms of casticin in GBM. The MTT assay and colony formation was used to evaluate the casticin-induced cell viability in GBM cells. Apoptosis was assessed by ANNEXIV/PI staining assay. Autophagy was analyzed by transmission electron microscopy and immunofluorescence assays. GBM stem cell (GSC) was analyzed by tumor-sphere formation assay and ALDEFLUOR assay. The anti-GBM effect of casticin was also determined by the U87MG xenograft model. Casticin inhibited tumor cell growth in vitro and in vivo, as well as significantly induced apoptosis and autophagy. Autophagy inhibition augmented casticin-induced apoptosis. Casticin also reduced the GSC population by suppressing Oct4, Nanog, and Sox2. Mechanistically, casticin inhibited Akt/mTOR and JAK2/STAT3 signal pathways. The antitumor effect of casticin in GBM was demonstrated by inducing apoptosis, autophagy, and reducing population of GSCs; thus, it may be a potential GBM therapeutic agent for future clinical usage.

apoptosis autophagy cancer stem cell casticin glioblastoma

SCI

English

Corresponding

Pharmacology & Pharmacy

Chemistry, Medicinal ; Pharmacology & Pharmacy

WOS:001089644600001

WILEY

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Dept Traumat Orthoped, 3002 Sungang West Rd, Shenzhen 518035, Peoples R China
2.Shenzhen Univ, Sch Biomed Engn, Med Sch, Shenzhen, Peoples R China
3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Spine Surg, Shanghai, Peoples R China
4.Shanxi Bethune Hosp, Dept Orthoped, Taiyuan, Peoples R China
5.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Hand & Microvasc Surg, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China
6.Southern Univ Sci & Technol, Affiliated Hosp 1, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China

Yang, Xun,Liu, Zeyuan,Xu, Xu,et al. Casticin induces apoptosis and cytoprotective autophagy while inhibiting stemness involving Akt/mTOR and JAK2/STAT3 pathways in glioblastoma[J]. PHYTOTHERAPY RESEARCH,2023.

Yang, Xun,Liu, Zeyuan,Xu, Xu,He, Meng,Xiong, Hongtao,&Liu, Lijun.(2023).Casticin induces apoptosis and cytoprotective autophagy while inhibiting stemness involving Akt/mTOR and JAK2/STAT3 pathways in glioblastoma.PHYTOTHERAPY RESEARCH.

Yang, Xun,et al."Casticin induces apoptosis and cytoprotective autophagy while inhibiting stemness involving Akt/mTOR and JAK2/STAT3 pathways in glioblastoma".PHYTOTHERAPY RESEARCH (2023).