Open Access

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

  • Published online on: November 3, 2021     https://doi.org/10.3892/or.2021.8217
  • Article Number: 6
  • Copyright: © Keeratichamroen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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