Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

  • Authors:
    • Zhi‑Ren Zhang
    • Ming‑Xia Gao
    • Kai Yang
  • View Affiliations

  • Published online on: June 6, 2017     https://doi.org/10.3892/etm.2017.4547
  • Pages: 805-812
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Abstract

Osteosarcoma (OS) is the most commonly diagnosed tumor of the bones in children and young adults. Even with conventional therapies the 5‑year survival rate is ~65% in patients with OS. Considering the side effects and aggressiveness of malignant bone tumors, research is focussing on multi‑targeted strategies in treatment. Cucurbitacin B, a triterpenoid compound has been demonstrated to induce apoptosis in various cancer cell types. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling cascades and mitogen activated protein kinases (MAPK) signalling cascades are critical regulators of tumorigenesis. The present study assessed the influence of cucurbitacin B on the viability and expression of MAPKs and proteins of the JAK2/STAT3 cascades in human OS cells (U‑2 OS). Cucurbitacin B (20‑100 µM) significantly reduced cell viability (P<0.05) and induced apoptosis, as assessed by MTT and Annexin V/propidium iodide staining, along with inhibiting cell migration. Gelatin zymography revealed supressed activities of matrix metalloproteinase (MMP‑)2 and 9. Furthermore, cucurbitacin B effectively upregulated the apoptotic pathway and caused the effective inhibition of MAPK signalling and JAK2/STAT3 cascades. Multifold suppression of vascular endothelial growth factor by cucurbitacin B was also observed, indicating inhibition of angiogenesis. Thus, by downregulating major pathways‑MAPK and JAK2/STAT3 and MMPs, cucurbitacin B has potent anti‑proliferative and anti‑metastatic effects that require further investigation with regards to cancer treatment.
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July-2017
Volume 14 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang ZR, Gao MX and Yang K: Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways. Exp Ther Med 14: 805-812, 2017
APA
Zhang, Z., Gao, M., & Yang, K. (2017). Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways. Experimental and Therapeutic Medicine, 14, 805-812. https://doi.org/10.3892/etm.2017.4547
MLA
Zhang, Z., Gao, M., Yang, K."Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways". Experimental and Therapeutic Medicine 14.1 (2017): 805-812.
Chicago
Zhang, Z., Gao, M., Yang, K."Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways". Experimental and Therapeutic Medicine 14, no. 1 (2017): 805-812. https://doi.org/10.3892/etm.2017.4547