Hellebrigenin Induces Apoptosis and Inhibits PI3K/AKT-Mediated Inflammation and Metastasis in Human Osteosarcoma Cells

Abarrategi A, Tornin J, Martinez-Cruzado L, Hamilton A, Martinez-Campos E, Rodrigo JP, González MV, Baldini N, Garcia-Castro J, Rodriguez R (2016) Osteosarcoma: cells-of-origin, cancer stem cells, and targeted therapies. Stem Cells Int 2016:3631764. https://doi.org/10.1155/2016/3631764

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abate ME, Longhi A, Galletti S, Ferrari S, Bacci G (2010) Non-metastatic osteosarcoma of the extremities in children aged 5 years or younger. PBC 55:652–654. https://doi.org/10.1002/pbc.22567

Article  Google Scholar 

Arun B, Goss P (2004) The role of COX-2 inhibition in breast cancer treatment and prevention. Semin Oncol 31:22–29. https://doi.org/10.1053/j.seminoncol.2004.03.042

Article  CAS  PubMed  Google Scholar 

Aziz SA, Davies M, Pick E, Zito C, Jilaveanu L, Camp RL, Rimm DL, Kluger Y, Kluger HM (2009) Phosphatidylinositol-3-kinase as a therapeutic target in melanoma. Clin Cancer Res 15:3029–3036. https://doi.org/10.1158/1078-0432.CCR-08-2768

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bacci G, Ferrari S, Lari S, Mercuri M, Donati D, Longhi A, Forni C, Bertoni F, Versari M, Pignotti E (2002) Osteosarcoma of the limb. Amputation or limb salvage in patients treated by neoadjuvant chemotherapy. J Bone Joint Surg Br 84:88–92. https://doi.org/10.1302/0301-620x.84b1.12211

Article  CAS  PubMed  Google Scholar 

Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P (2006) Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 106:1154–1161. https://doi.org/10.1002/cncr.21724

Article  PubMed  Google Scholar 

Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545. https://doi.org/10.1016/S0140-6736(00)04046-0

Article  CAS  PubMed  Google Scholar 

Beird HC, Bielack SS, Flanagan AM, Gill J, Heymann D, Janeway KA, Livingston JA, Roberts RD, Strauss SJ, Gorlick R (2022) Osteosarcoma. Nat Rev Dis Primers 8(1):77. https://doi.org/10.1038/s41572-022-00409-y

Article  PubMed  Google Scholar 

Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 20:776–790. https://doi.org/10.1200/JCO.2002.20.3.776

Article  PubMed  Google Scholar 

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 7:248–254. https://doi.org/10.1016/0003-2697(76)90527-3

Article  Google Scholar 

Cao SS, Kaufman RJ (2014) Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid Redox Signal 21:396–413. https://doi.org/10.1089/ars.2014.5851

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cavalcanti BC, Soares BM, Barreto FS, Magalhães HIF, Ferreira JRO, Almeida ATA, Araújo Beserra Filho JI, Silva J, Dos Santos HS, Marinho ES, Furtado CLM, Moraes Filho MO, Pessoa C, Ferreira PMP (2024) Hellebrigenin triggers death of promyelocytic leukemia cells by non-genotoxic ways. Toxicon 238:107591. https://doi.org/10.1016/j.toxicon.2023.107591

Article  CAS  PubMed  Google Scholar 

Chaudhry GE, Md Akim A, Sung YY, Sifzizul TMT (2022) Cancer and apoptosis: the apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics. Front Pharmacol 13:842376. https://doi.org/10.3389/fphar.2022.842376

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crusz SM, Balkwill FR (2015) Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol 12:584–596. https://doi.org/10.1038/nrclinonc.2015.105

Article  CAS  PubMed  Google Scholar 

Dong Z, Feng L, Chao Y, Hao Y, Chen M, Gong F, Han X, Zhang R, Cheng L, Liu Z (2019) Amplification of tumor oxidative stresses with liposomal fenton catalyst and glutathione inhibitor for enhanced cancer chemotherapy and radiotherapy. Nano Lett 19:805–815. https://doi.org/10.1021/acs.nanolett.8b03905

Article  CAS  PubMed  Google Scholar 

Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6

Article  CAS  PubMed  Google Scholar 

Ferrari S, Serra M (2015) An update on chemotherapy for osteosarcoma. Expert Opin Pharmacother 16:2727–2736. https://doi.org/10.1517/14656566.2015.1102226

Article  CAS  PubMed  Google Scholar 

Friebele JC, Peck J, Pan X, Abdel-Rasoul M, Mayerson JL (2015) Osteosarcoma: a meta-analysis and review of the literature. Am J Orthop (Belle Mead NJ) 44:547–553

PubMed  Google Scholar 

Gao S, Chen T, Choi MY, Liang Y, Xue J, Wong YS (2013) Cyanidin reverses cisplatin-induced apoptosis in HK-2 proximal tubular cells through inhibition of ROS-mediated DNA damage and modulation of the ERK and AKT pathways. Cancer Lett 333:36–46. https://doi.org/10.1016/j.canlet.2012.12.029

Article  CAS  PubMed  Google Scholar 

García JG, Ansorena E, Izal I, Zalba G, De Miguel C, Milagro FI (2023) Structure, regulation, and physiological functions of NADPH oxidase 5 (NOX5). J Physiol Biochem 79:383–395. https://doi.org/10.1007/s13105-023-00955-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Geller DS, Gorlick R (2010) Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol 8:705–718

PubMed  Google Scholar 

Han L, Yuan B, Shimada R, Hayashi H, Si N, Zhao HY, Bian B, Takagi N (2018) Cytocidal effects of arenobufagin and hellebrigenin, two active bufadienolide compounds, against human glioblastoma cell line U-87. Int J Oncol 53:2488–2502. https://doi.org/10.3892/ijo.2018.4567

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harvei S, Solheim Ø (1981) The prognosis in osteosarcoma: Norwegian national data. Cancer 48:1719–1723. https://doi.org/10.1002/1097-0142(19811015)48:8%3c1719::aid-cncr2820480806%3e3.0.co;2-j

Article  CAS  PubMed  Google Scholar 

Hassannia B, Vandenabeele P, Vanden Berghe T (2019) Targeting ferroptosis to iron out cancer. Cancer Cell 35:830–849. https://doi.org/10.1016/j.ccell.2019.04.002

Article  CAS  PubMed  Google Scholar 

Haynes CM, Titus EA, Cooper AA (2004) Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death. Mol Cell 15:767–776. https://doi.org/10.1016/j.molcel.2004.08.025

Article  CAS  PubMed  Google Scholar 

He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, Li B (2021) Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther 6:425. https://doi.org/10.1038/s41392-021-00828-5

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4:988–1004. https://doi.org/10.1038/nrd1902

Article  CAS  PubMed  Google Scholar 

Ho HY, Chen MK, Tsai YJ, Lin CC, Lo YS, Chuang YC, Hsieh MJ (2025) The efficacy of hellebrigenin against nasopharyngeal carcinoma cells: the molecular and bioinformatic analysis. J Cell Mol Med 29:e70624. https://doi.org/10.1111/jcmm.70624

Article  CAS  PubMed  PubMed Central 

Comments (0)

No login
gif