OncoTargets and Therapy (Nov 2022)
7β-22 Dihydroxyhopane, Isolated from the Sub-Antarctic Lichen, Inhibits the Viability and Stemness in Glioma Stem Like Cells
Abstract
Hyun-Jin Kim,1,* Sung-Suk Suh,2,* Jeongwon Park,3 Min-Ji Shin,2 Man Hyung Koo,4 Suk Jun Lee,5 Young-Jun Jeon,6 Seongsoo Lee,3 Ui-Joung Youn,7 Sung-Hak Kim1 1Department of Animal Science, Chonnam National University, Gwangju, 61186, Korea; 2Department of Biosciences, Mokpo National University, Muan, 58554, Korea; 3Gwangju Center, Korea Basic Science Institute (KBSI), Gwangju, 61186, Korea; 4Research Unit of Cryogenic Novel Material, Korea Polar Research Institute, Incheon, 21990, Korea; 5Department of Biomedical Laboratory Science, College of Health & Medical Sciences, Cheongju University, Chungbuk, 28503, Korea; 6Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea; 7Division of Life Sciences, Korea Polar Research Institute (KOPRI), Incheon, 21990, Korea*These authors contributed equally to this workCorrespondence: Ui-Joung Youn, Division of Life Sciences, Korea Polar Research Institute (KOPRI), Incheon, 21990, Korea, Tel +82 32 760 5562, Email [email protected] Sung-Hak Kim, Department of Animal Science, Chonnam National University, Gwangju, 61186, Korea, Tel +82 62 530 2115, Email [email protected]: Glioma stem cells (GSCs) have been reported to contribute to tumor initiation and relapse, therapy resistance, and intra-tumoral heterogeneity of glioblastoma multiforme. Therefore, inhibiting GSCs presents a critical therapeutic tactic to suppress the aggressiveness of tumors.Methods: In this study, we examined the effects of 7β-22 dihydroxyhopane (AP 18), isolated from the sub-Antarctic lichen, Pseudocyphellaria freycinetii. The cytotoxic effect of AP 18 and its effects on cell proliferation were assessed by alamarBlue assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Real-time confluence analysis was performed with a Celloger automatic live cell imaging system. Western Blotting and 3-D optical diffraction tomography (ODT) imaging were performed to determine whether apoptosis was triggered by AP 18. A Limiting dilution assay and qRT-PCR were performed to investigate the impact of AP 18 on GSC stemness.Results: AP 18 significantly reduced GSCs viability and proliferation, inducing programmed cell death identified by Annexin V/PI staining and had effects on morphologic features determined by 3-D ODT. Interestingly, treatment with AP 18 suppressed stemness features.Conclusion: Taken together, our results suggest that AP 18 might be a potential therapeutic agent to target GSCs.Keywords: Glioblastoma, glioma, Pseudocyphellaria freycinetii, hopane triterpenoid
