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JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from Gymnanthemum extensum on A549 human lung carcinoma cells

  • Authors:
    • Siriporn Keeratichamroen
    • Kriengsak Lirdprapamongkol
    • Sanit Thongnest
    • Jutatip Boonsombat
    • Pornsuda Chawengrum
    • Thiwaree Sornprachum
    • Jitnapa Sirirak
    • Chris Verathamjamras
    • Narittira Ornnork
    • Somsak Ruchirawat
    • Jisnuson Svasti
  • View Affiliations / Copyright

    Affiliations: Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand, Laboratory of Natural Products, Chulabhorn Research Institute, Bangkok 10210, Thailand, Program in Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand, Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand, Center of Excellence on Environmental Health and Toxicology, Ministry of Education, Bangkok 10400, Thailand
    Copyright: © Keeratichamroen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 6
    |
    Published online on: November 3, 2021
       https://doi.org/10.3892/or.2021.8217
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Abstract

Due to drug resistance and disease recurrence, lung cancer remains one of the primary cancer‑related causes of death in both men and women worldwide. In addition, lung cancer is clinically silent and thus most patients are at an advanced stage at the time of diagnosis. The limited efficiency of current conventional chemotherapies necessitates the search for novel effective anticancer agents. The present study demonstrated the anti‑proliferative effect and apoptosis‑inducing activity of three sesquiterpene lactones isolated from Gymnanthemum extensum, vernodalin (VDa), vernolepin (VLe) and vernolide (VLi), on A549 human lung cancer cells. Treatment with sub‑cytotoxic doses (cell viability remaining >75%) of VDa, VLe and VLi, arrested progression of the A549 cell cycle at the G0/G1 phase, while cytotoxic doses of the three compounds induced G2/M phase arrest and apoptosis. Mechanistic studies revealed that VDa, VLe and VLi may exert their anti‑tumor activity through the JAK2/STAT3 pathway. Molecular docking analysis confirmed that VDa, VLe and VLi formed hydrogen bonds with the FERM domain of JAK2 protein. Overall, the present study highlighted the potential therapeutic value of VDa, VLe and VLi to be further developed as anticancer agents for the treatment of lung cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Keeratichamroen S, Lirdprapamongkol K, Thongnest S, Boonsombat J, Chawengrum P, Sornprachum T, Sirirak J, Verathamjamras C, Ornnork N, Ruchirawat S, Ruchirawat S, et al: JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells. Oncol Rep 47: 6, 2022.
APA
Keeratichamroen, S., Lirdprapamongkol, K., Thongnest, S., Boonsombat, J., Chawengrum, P., Sornprachum, T. ... Svasti, J. (2022). JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells. Oncology Reports, 47, 6. https://doi.org/10.3892/or.2021.8217
MLA
Keeratichamroen, S., Lirdprapamongkol, K., Thongnest, S., Boonsombat, J., Chawengrum, P., Sornprachum, T., Sirirak, J., Verathamjamras, C., Ornnork, N., Ruchirawat, S., Svasti, J."JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells". Oncology Reports 47.1 (2022): 6.
Chicago
Keeratichamroen, S., Lirdprapamongkol, K., Thongnest, S., Boonsombat, J., Chawengrum, P., Sornprachum, T., Sirirak, J., Verathamjamras, C., Ornnork, N., Ruchirawat, S., Svasti, J."JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells". Oncology Reports 47, no. 1 (2022): 6. https://doi.org/10.3892/or.2021.8217
Copy and paste a formatted citation
x
Spandidos Publications style
Keeratichamroen S, Lirdprapamongkol K, Thongnest S, Boonsombat J, Chawengrum P, Sornprachum T, Sirirak J, Verathamjamras C, Ornnork N, Ruchirawat S, Ruchirawat S, et al: JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells. Oncol Rep 47: 6, 2022.
APA
Keeratichamroen, S., Lirdprapamongkol, K., Thongnest, S., Boonsombat, J., Chawengrum, P., Sornprachum, T. ... Svasti, J. (2022). JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells. Oncology Reports, 47, 6. https://doi.org/10.3892/or.2021.8217
MLA
Keeratichamroen, S., Lirdprapamongkol, K., Thongnest, S., Boonsombat, J., Chawengrum, P., Sornprachum, T., Sirirak, J., Verathamjamras, C., Ornnork, N., Ruchirawat, S., Svasti, J."JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells". Oncology Reports 47.1 (2022): 6.
Chicago
Keeratichamroen, S., Lirdprapamongkol, K., Thongnest, S., Boonsombat, J., Chawengrum, P., Sornprachum, T., Sirirak, J., Verathamjamras, C., Ornnork, N., Ruchirawat, S., Svasti, J."JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <em>Gymnanthemum extensum</em> on A549 human lung carcinoma cells". Oncology Reports 47, no. 1 (2022): 6. https://doi.org/10.3892/or.2021.8217
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