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Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway

journal contribution
submitted on 2023-10-18, 10:54 and posted on 2023-10-19, 04:31 authored by Kirti.S. Prabhu, Ajaz A. Bhat, Kodappully S. Siveen, Shilpa Kuttikrishnan, Syed Shadab Raza, Thesni Raheed, Anh Jochebeth, Abdul Q. Khan, M.Zafar Chawdhery, Mohammad Haris, Michal Kulinski, Said Dermime, Martin Steinhoff, Shahab Uddin

Effective treatment of lung cancer remains a significant clinical challenge due to its multidrug resistance and side effects of the current treatment options. The high mortality associated with this malignancy indicates the need for new therapeutic interventions with fewer side effects. Natural compounds offer various benefits such as easy access, minimal side effects, and multi-molecular targets and thus, can prove useful in treating lung cancer. Sanguinarine (SNG), a natural compound, possesses favorable therapeutic potential against a variety of cancers. Here, we examined the underlying molecular mechanisms of SNG in Non-Small Cell Lung Cancer (NSCLC) cells. SNG suppressed cell growth and induced apoptosis via downregulation of the constitutively active JAK/STAT pathway in all the NSCLC cell lines. siRNA silencing of STAT3 in NSCLC cells further confirmed the involvement of the JAK/STAT signaling cascade. SNG treatment increased Bax/Bcl-2 ratio, which contributed to a leaky mitochondrial membrane leading to cytochrome c release accompanied by caspase activation. In addition, we established the antitumor effects of SNG through reactive oxygen species (ROS) production, as inhibiting ROS production prevented the apoptosis-inducing potential of SNG. In vivo xenograft tumor model further validated our in vitro findings. Overall, our study investigated the molecular mechanisms by which SNG induces apoptosis in NSCLC, providing avenues for developing novel natural compound-based cancer therapies.

Other Information

Published in: Biomedicine & Pharmacotherapy
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Open Access funding provided by the Qatar National Library



  • English



Publication Year

  • 2021

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Hamad Medical Corporation
  • Interim Translational Research Institute - HMC
  • National Center for Cancer Care and Research - HMC
  • Qatar University
  • Laboratory Animal Research Center - QU
  • Sidra Medicine
  • Weill Cornell Medicine - Qatar