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

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 comp...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Apoptosis Antiproliferative Alkaloids Antioxidants Cancer stem cells Sanguinarine Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/65d7433946d144e296f1d326094998de
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spelling	oai:doaj.org-article:65d7433946d144e296f1d326094998de2021-11-14T04:30:18ZSanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway0753-332210.1016/j.biopha.2021.112358https://doaj.org/article/65d7433946d144e296f1d326094998de2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011422https://doaj.org/toc/0753-3322Effective 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.Kirti.S. PrabhuAjaz A. BhatKodappully S. SiveenShilpa KuttikrishnanSyed Shadab RazaThesni RaheedAnh JochebethAbdul Q. KhanM.Zafar ChawdheryMohammad HarisMichal KulinskiSaid DermimeMartin SteinhoffShahab UddinElsevierarticleApoptosisAntiproliferativeAlkaloidsAntioxidantsCancer stem cellsSanguinarineTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112358- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Apoptosis Antiproliferative Alkaloids Antioxidants Cancer stem cells Sanguinarine Therapeutics. Pharmacology RM1-950
spellingShingle	Apoptosis Antiproliferative Alkaloids Antioxidants Cancer stem cells Sanguinarine Therapeutics. Pharmacology RM1-950 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 Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
description	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.
format	article
author	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
author_facet	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
author_sort	Kirti.S. Prabhu
title	Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
title_short	Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
title_full	Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
title_fullStr	Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
title_full_unstemmed	Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
title_sort	sanguinarine mediated apoptosis in non-small cell lung cancer via generation of reactive oxygen species and suppression of jak/stat pathway
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/65d7433946d144e296f1d326094998de
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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

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