Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Osmundacetone Inhibits Angiogenesis of Infantile Hemangiomas through Inducing Caspases and Reducing VEGFR2/MMP9

Author(s): Chen Ke, Changhan Chen, Ming Yang, Hao Chen, Liqun Li* and Youhui Ke*

Volume 24, Issue 2, 2024

Published on: 08 November, 2023

Page: [125 - 131] Pages: 7

DOI: 10.2174/0118715206273410231103100600

Price: $65

Abstract

Aim: This study aims to explore the potential of Osmundacetone (OSC) as a new treatment for infantile hemangiomas (IH), the most common benign tumors in infancy. Currently, propranolol serves as the primary treatment for IH, but its effectiveness is limited, and it poses challenges of drug resistance and side effects. Therefore, there is a pressing need to identify alternative therapies for IH.

Methods: The effects of OSC on the proliferation and apoptosis of HemECs (endothelial cells from hemangiomas) were assessed using CCK-8 assay, colony formation assay, HOCHEST 33342 staining, and flow cytometry. Western blot analysis was performed to investigate OSC's influence on Caspases and angiogenesis-related proteins. Animal models were established using HemECs and BALB/c mice, and histological and immunohistochemical staining were conducted to evaluate the impact of OSC on mouse hemangiomas, VEGFR2, and MMP9 expression.

Results: OSC treatment significantly reduced HemECs' viability and colony-forming ability, while promoting apoptosis, as indicated by increased HOCHEST 33342 staining. OSC upregulated the protein expression of Bax, PARP, Caspase9, Caspase3, AIF, Cyto C, FADD, and Caspase8 in HemECs. In animal models, OSC treatment effectively reduced hemangioma size and improved histopathological changes. OSC also suppressed VEGFR2 and MMP9 expression while elevating Caspase3 levels in mouse hemangiomas.

Conclusion: OSC demonstrated promising results in inhibiting HemECs' proliferation, inducing apoptosis, and ameliorating pathological changes in hemangiomas in mice. Moreover, it influenced the expression of crucial caspases and angiogenesis-related proteins. These findings suggest that OSC holds potential as a novel drug for clinical treatment of IH.

« Previous Next »
Graphical Abstract

[1]
Torrence, D.; Antonescu, C.R. The genetics of vascular tumours: An update. Histopathology, 2022, 80(1), 19-32.
[http://dx.doi.org/10.1111/his.14458] [PMID: 34958509]
[2]
Hasbani, D.J.; Hamie, L. Infantile Hemangiomas. Dermatol. Clin., 2022, 40(4), 383-392.
[http://dx.doi.org/10.1016/j.det.2022.06.004] [PMID: 36243426]
[3]
Sebaratnam, D.F.; Rodríguez, B.A.; Wong, L.C.F.; Wargon, O. Infantile hemangioma. Part 2: Management. J. Am. Acad. Dermatol., 2021, 85(6), 1395-1404.
[http://dx.doi.org/10.1016/j.jaad.2021.08.020] [PMID: 34419523]
[4]
Krowchuk, D.P.; Frieden, I.J.; Mancini, A.J.; Darrow, D.H.; Blei, F.; Greene, A.K.; Annam, A.; Baker, C.N.; Frommelt, P.C.; Hodak, A.; Pate, B.M.; Pelletier, J.L.; Sandrock, D.; Weinberg, S.T.; Whelan, M.A. Clinical practice guideline for the management of infantile hemangiomas. Pediatrics, 2019, 143(1), e20183475.
[http://dx.doi.org/10.1542/peds.2018-3475] [PMID: 30584062]
[5]
Zhang, J.; Li, Y.; Zhang, B.; Chen, K.; Wang, Q.; Li, Z.; Sun, S.; Tian, J.; Sun, X.; Yao, C.; Xie, Y.; Hu, J.; Tian, J.; Zhan, S.; Liu, J.; Wu, J.; Sun, F.; Du, L.; Yu, J.; Zhang, Y.; Zhang, L.; Gao, R.; Wang, B.; Tang, J.; Zhu, M.; Mao, J.; Huang, Y.; Zheng, W.; Yang, F.; Pang, B. Evidence‐based traditional Chinese medicine research: Beijing declaration. J. Evid. Based Med., 2020, 13(2), 91-92.
[http://dx.doi.org/10.1111/jebm.12389] [PMID: 32470228]
[6]
Lu, Y.; Jia, Y.; Xue, Z.; Li, N.; Liu, J.; Chen, H. Recent developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, structural characteristics, biological activities and application. Polymers, 2021, 13(9), 1441.
[http://dx.doi.org/10.3390/polym13091441] [PMID: 33947037]
[7]
Béni, Z.; Dékány, M.; Sárközy, A.; Kincses, A.; Spengler, G.; Papp, V.; Hohmann, J.; Ványolós, A. Triterpenes and phenolic compounds from the fungus Fuscoporia torulosa: Isolation, structure determination and biological activity. Molecules, 2021, 26(6), 1657.
[http://dx.doi.org/10.3390/molecules26061657] [PMID: 33809760]
[8]
Yang, Y.; He, P.; Hou, Y.; Liu, Z.; Zhang, X.; Li, N. Osmundacetone modulates mitochondrial metabolism in non-small cell lung cancer cells by hijacking the glutamine/glutamate/α-KG metabolic axis. Phytomedicine, 2022, 100, 154075.
[http://dx.doi.org/10.1016/j.phymed.2022.154075] [PMID: 35413646]
[9]
Kowalska, M. Dębek, W.; Matuszczak, E. Infantile Hemangiomas: An update on pathogenesis and treatment. J. Clin. Med., 2021, 10(20), 4631.
[http://dx.doi.org/10.3390/jcm10204631] [PMID: 34682753]
[10]
Van Opdenbosch, N.; Lamkanfi, M. Caspases in cell death, inflammation, and disease. Immunity, 2019, 50(6), 1352-1364.
[http://dx.doi.org/10.1016/j.immuni.2019.05.020] [PMID: 31216460]
[11]
Léauté-Labrèze, C.; de la Roque, E.D.; Hubiche, T.; Boralevi, F.; Thambo, J.B.; Taïeb, A. Propranolol for severe hemangiomas of infancy. N. Engl. J. Med., 2008, 358(24), 2649-2651.
[http://dx.doi.org/10.1056/NEJMc0708819] [PMID: 18550886]
[12]
Chang, L.; Lv, D.; Yu, Z.; Ma, G.; Ying, H.; Qiu, Y.; Gu, Y.; Jin, Y.; Chen, H.; Lin, X. Infantile hemangioma: factors causing recurrence after propranolol treatment. Pediatric Res., 2018, 83(1-1), 175-182.
[http://dx.doi.org/10.1038/pr.2017.220]
[13]
Gomez-Acevedo, H.; Dai, Y.; Strub, G.; Shawber, C.; Wu, J.K.; Richter, G.T. Identification of putative biomarkers for Infantile Hemangiomas and Propranolol treatment via data integration. Sci. Rep., 2020, 10(1), 3261.
[http://dx.doi.org/10.1038/s41598-020-60025-2] [PMID: 32094357]
[14]
Green, D.R. Caspases and Their Substrates. Cold Spring Harb. Perspect. Biol., 2022, 14(3), 041012.
[http://dx.doi.org/10.1101/cshperspect.a041012] [PMID: 35232877]
[15]
Kesavardhana, S.; Malireddi, R.K.S.; Kanneganti, T.D. Caspases in cell death, inflammation, and pyroptosis. Annu. Rev. Immunol., 2020, 38(1), 567-595.
[http://dx.doi.org/10.1146/annurev-immunol-073119-095439] [PMID: 32017655]
[16]
Bertheloot, D.; Latz, E.; Franklin, B.S. Necroptosis, pyroptosis and apoptosis: An intricate game of cell death. Cell. Mol. Immunol., 2021, 18(5), 1106-1121.
[http://dx.doi.org/10.1038/s41423-020-00630-3] [PMID: 33785842]
[17]
Zhang, Y.; Wang, M.; Zhang, X.; Jiang, Z.; Zhang, Y.; Fu, X.; Li, Y.; Cao, D.; Han, J.; Tong, J. Helicid improves lipopolysaccharide-induced apoptosis of C6 cells by regulating SH2D5 DNA methylation via the CytC/Caspase9/Caspase3 signaling pathway. Contrast Media Mol. Imaging, 2022, 2022, 1-13.
[http://dx.doi.org/10.1155/2022/9242827] [PMID: 35173561]
[18]
Duan, C.; Kuang, L.; Hong, C.; Xiang, X.; Liu, J.; Li, Q.; Peng, X.; Zhou, Y.; Wang, H.; Liu, L.; Li, T. Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2. Cell Death Dis., 2021, 12(11), 1050.
[http://dx.doi.org/10.1038/s41419-021-04343-x] [PMID: 34741026]
[19]
Mandal, R.; Barrón, J.C.; Kostova, I.; Becker, S.; Strebhardt, K. Caspase-8: The double-edged sword. Biochim. Biophys. Acta Rev. Cancer, 2020, 1873(2), 188357.
[http://dx.doi.org/10.1016/j.bbcan.2020.188357] [PMID: 32147543]
[20]
Luo, Q.; Wu, X.; Zhao, P.; Nan, Y.; Chang, W.; Zhu, X.; Su, D.; Liu, Z. OTUD1 activates caspase‐independent and caspase‐dependent apoptosis by promoting AIF nuclear translocation and MCL1 degradation. Adv. Sci. (Weinh.), 2021, 8(8), 2002874.
[http://dx.doi.org/10.1002/advs.202002874] [PMID: 33898171]
[21]
Wu, S.W.; Su, C.H.; Ho, Y.C.; Huang-Liu, R.; Tseng, C.C.; Chiang, Y.W.; Yeh, K.L.; Lee, S.S.; Chen, W.Y.; Chen, C.J.; Li, Y.C.; Lee, C.Y.; Kuan, Y.H. Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage. Ecotoxicol. Environ. Saf., 2021, 213, 112062.
[http://dx.doi.org/10.1016/j.ecoenv.2021.112062] [PMID: 33618169]
[22]
Apte, R.S.; Chen, D.S.; Ferrara, N. VEGF in signaling and disease: Beyond discovery and development. Cell, 2019, 176(6), 1248-1264.
[http://dx.doi.org/10.1016/j.cell.2019.01.021] [PMID: 30849371]
[23]
Porta, M.; Striglia, E. Intravitreal anti-VEGF agents and cardiovascular risk. Intern. Emerg. Med., 2020, 15(2), 199-210.
[http://dx.doi.org/10.1007/s11739-019-02253-7] [PMID: 31848994]
[24]
DiStefano, P.V.; Glading, A.J. VEGF signalling enhances lesion burden in KRIT1 deficient mice. J. Cell. Mol. Med., 2020, 24(1), 632-639.
[http://dx.doi.org/10.1111/jcmm.14773] [PMID: 31746130]
[25]
Mondal, S.; Adhikari, N.; Banerjee, S.; Amin, S.A.; Jha, T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur. J. Med. Chem., 2020, 194, 112260.
[http://dx.doi.org/10.1016/j.ejmech.2020.112260] [PMID: 32224379]
[26]
Huang, L.J.; Li, G.; Ding, Y.; Sun, J.H.; Wu, T.T.; Zhao, W.; Zeng, Y.S. LINGO-1 deficiency promotes nerve regeneration through reduction of cell apoptosis, inflammation, and glial scar after spinal cord injury in mice. Exp. Neurol., 2019, 320, 112965.
[http://dx.doi.org/10.1016/j.expneurol.2019.112965] [PMID: 31132364]
[27]
Li, H.; Cai, E.; Cheng, H.; Ye, X.; Ma, R.; Zhu, H.; Chang, X. FGA controls VEGFA secretion to promote angiogenesis by activating the VEGFR2-FAK signalling pathway. Front. Endocrinol., 2022, 13, 791860.
[http://dx.doi.org/10.3389/fendo.2022.791860] [PMID: 35498401]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy