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Jolkinolide B attenuates laryngeal cancer cell growth and induces apoptosis via PTEN/PI3K/Akt signaling pathway

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Abstract

Jolkinolide B (JB) is a bioactive diterpenoid, isolated from the root of Euphorbia fischeriana Steud, and has been reported to have anti-tumor and anti-inflammation function by regulation of cell migration, invasion, apoptosis, and cell cycle. We aimed to evaluate the effect of JB on laryngeal cancer cells. Human normal larynx epithelial (HBE) cells and cancer cell lines TU212, TU177, and Hep-2 were cultured; MTT assay was used to assess cell proliferation. LY294002 (a PI3K/Akt inhibitor) and IGF-1 (a PI3K/Akt activator) were employed to investigate the expression of PI3K/Akt pathway. Cell migration and invasion activities were detected by scratch wound healing and transwell assay, respectively. Flow cytometry assay was used to assess cell apoptosis. The expression levels of proteins were assessed by immunofluorescence and Western blotting assay. JB inhibited TU212, TU177, and Hep-2 cell viability with an IC50 value of 54.57 ± 0.53 μg/mL, 44.82 ± 0.32 μg/mL, and 49.63 ± 0.47 μg/mL, respectively. Compared with control group, the proliferation, migration, and invasion of cells significantly decreased after JB and LY294002 treatment, while cell apoptosis increased. In IGF-1 group, the results were opposite compared to the JB and LY294002 groups. Western blotting results showed that JB and LY294002 treatment significantly inhibited the levels of Bcl-2, p-PI3K, and p-Akt while the levels of Bax, cleaved caspase-3, and PTEN protein significantly increased. Our study suggested that JB exhibits an inhibition effect on laryngeal cancer cell growth in vitro.

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References

  • Abu El-Asrar AM, Ahmad A, Alam K, Siddiquei MM, Mohammad G, Hertogh GD, Mousa A, Opdenakker G (2017) Extracellular matrix metalloproteinase inducer (EMMPRIN) is a potential biomarker of angiogenesis in proliferative diabetic retinopathy. Acta Ophthalmol 95(7):697–704

    Article  CAS  Google Scholar 

  • Aghdaei HA, Kadijani AA, Sorrentino D, Mirzaei A, Shahrokh S, Balaii H, Geraci M, Zail MR (2018) An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients. United European Gastroenterol J 6(7):1074–1081

    Article  CAS  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre LA, Jemal A (2018) Global Cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  Google Scholar 

  • Costa RLB, Han HS, Gradishar WJ (2018) Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review. Breast Cancer Res Treat 169(3):397–406

    Article  CAS  Google Scholar 

  • Gao X, Han H (2018) Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non-small cell lung cancer cells. J Cell Biochem 119(6):4967–4974

    Article  CAS  Google Scholar 

  • Gao C, Yan X, Wang B, Yu L, Han J, Li D, Zheng Q (2016) Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis. Sci Rep 6:36114

    Article  CAS  Google Scholar 

  • Han MH, Lee WS, Nagappan A, Kim HJ, Park C, Kim GY, Hong SH, Kim ND, Ryu CH, Shin SC, Choi YH (2016) Polyphenols from Korean prostrate spurge Euphorbia supina induce apoptosis through the fas-associated extrinsic pathway and activation of ERK in human leukemic U937 cells. Oncol Rep 36(1):99–107

    Article  CAS  Google Scholar 

  • Li Y, Liu XL, Cai ZG, Zhang SX (2014) LC-ESI-MS/MS analysis and pharmacokinetics of jolkinolide B, a potential antitumor active component isolated from Euphorbia fischeriana, in rat plasma. Biomed Chromatogr 28(2):193–196

    Article  CAS  Google Scholar 

  • Lin Y, Cui H, Xu H, Yue L, Xu H, Jiang L, Liu J (2012) Jolkinolide B induces apoptosis in MDA-MB-231 cells through inhibition of the PI3K/Akt signaling pathway. Oncol Rep 27(6):1976–1980

    CAS  PubMed  Google Scholar 

  • Liu JC, Sun YX, Liu L, Yu C (2012) A water-soluble polysaccharide (EFP-AW1) from the alkaline extract of the roots of a traditional Chinese medicine, Euphorbia fischeriana: fraction and characterization. Carbohydr Polym 88(4):1299–1303

    Article  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Paez J, Sellers WR (2003) PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res 115:145–167

    Article  CAS  Google Scholar 

  • Pan H, Li T, Jiang Y, Pan C, Ding Y, Huang Z, Yu H, Kong D (2018) Overexpression of circular RNA ciRS-7 abrogates the tumor suppressive effect of miR-7 on gastric cancer via PTEN/PI3K/AKT signaling pathway. J Cell Biochem 119(1):440–446

    Article  CAS  Google Scholar 

  • Rogers C, Fernandes-Alnemri T, Mayes L, Alnemri D, Cingolani G, Alnemri E (2017) Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat Commun 8:14128

    Article  CAS  Google Scholar 

  • Starska K, Forma E, Lewy-Trenda I, Stasikowska-Kanicka O, Skóra M, Bryś M (2018) Fibroblast growth factor receptor 1 and 3 expression is associated with regulatory PI3K/AKT kinase activity, as well as invasion and prognosis, in human laryngeal cancer. Cell Oncol (dordr) 41(3):253–268

    Article  CAS  Google Scholar 

  • Uren RT, O’Hely M, Iyer S, Bartolo R, Shi MX, Brouwer JM, Alsop AE, Dewson G, Kluck RM (2017) Disordered clusters of Bak dimers rupture mitochondria during apoptosis. Elife 6:e19944

  • Vasas A, Hohmann J (2014) Euphorbia diterpenes: isolation, structure, biological activity, and synthesis (2008–2012). Chem Rev 114(17):8579–8612

    Article  CAS  Google Scholar 

  • Very N, Vercoutter-Edouart AS, Lefebvre T, Hardivillé S, Yazidi-Belkoura IE (2018) Cross-dysregulation of O-glcNAcylation and PI3K/AKT/mTOR Axis in human chronic diseases. Front Endocrinol (lausanne) 9:602

    Article  Google Scholar 

  • Walter M, Simanovich E, Brod V, Lahat N, Bitterman H, Rahat MA (2015) An epitope-specific novel anti-EMMPRIN polyclonal antibody inhibits tumor progression. Oncoimmunology 5(2):e1078056

  • Wan G, Zhou L, Xie M, Chen H, Tian J (2010) Characterization of side population cells from laryngeal cancer cell lines. Head Neck 32:1302–1309

    Article  Google Scholar 

  • Wang J, Wu Y, Gao W, Li F, Bo Y, Zhu M, Fu R, Liu Q, Wen S, Wang B (2017) Identification and characterization of cd133+cd44+ cancer stem cells from human laryngeal squamous cell carcinoma cell lines. J Cancer 8:497–506

    Article  Google Scholar 

  • Xu HY, Chen ZW, Hou JC, Du FX, Liu JC (2013) Jolkinolide B induces apoptosis in MCF-7 cells through inhibition of the PI3K/Akt/mTOR signaling pathway. Oncol Rep 29(1):212–218

    Article  CAS  Google Scholar 

  • Yang T, Li S, Liu J, Yin D, Yang X, Tang Q (2018) LncRNA-NKILA/NF-κB feedback loop modulates laryngeal cancer cell proliferation, invasion, and radioresistance. Cancer Med 7:2048–2063

    Article  CAS  Google Scholar 

  • Yang H, Li Y, Huo P, Li XO, Kong D, Mu W, Fang W, Li L, Liu N, Fang L, Li H, He C (2015) Protective effect of jolkinolide B on LPS-induced mouse acute lung injury. Int Immunopharmacol 26(1):119–124

    Article  CAS  Google Scholar 

  • Ye D, Zhou C, Deng H, Lin L, Zhou S (2019) MicroRNA-145 inhibits growth of laryngeal squamous cell carcinoma by targeting the PI3K/Akt signaling pathway. Cancer Manag Res 11:3801–3812

    Article  CAS  Google Scholar 

  • Zhang R, Li G, Zhang Q, Tang Q, Huang J, Hu C, Liu Y, Wang Q, Liu W, Gao N, Zhou S (2018) Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells. Cell Death Dis 9(6):598

    Article  Google Scholar 

  • Zhu Y, Yan L, Zhu W, Song X, Yang G, Wang S (2019) MMP2/3 promote the growth and migration of laryngeal squamous cell carcinoma via PI3K/Akt-NF-κB-mediated epithelial-mesenchymal transformation. J Cell Physiol. https://doi.org/10.1002/jcp.28242

    Article  PubMed  PubMed Central  Google Scholar 

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    Authors and Affiliations

    1. Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, No. 20 Yuhuangding East Road, Yantai, 264000, Shandong, China

      Lei Dong, Feifei Liu, Dawei Liu, Shasha Kang & Xin Yang

    2. Department of Otorhinolaryngology, Yantai Haigang Hospital, No. 100 Xingfu Road, Zhifu District, Yantai, 264000, Shandong, China

      Junxia Wang

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    1. Lei Dong
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    5. Xin Yang
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    Correspondence to Xin Yang or Junxia Wang.

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    Lei Dong and Feifei Liu contributed equally to this work.

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    Dong, L., Liu, F., Liu, D. et al. Jolkinolide B attenuates laryngeal cancer cell growth and induces apoptosis via PTEN/PI3K/Akt signaling pathway. In Vitro Cell.Dev.Biol.-Animal 57, 786–794 (2021). https://doi.org/10.1007/s11626-021-00612-3

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