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Open AccessArticle

Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species

1
Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar
2
Department of Lab Medicine and Pathology, Hamad Medical Corporation, Doha 3050, Qatar
3
Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha 3050, Qatar
4
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA
*
Authors to whom correspondence should be addressed.
The authors contribute equally.
Molecules 2020, 25(5), 1229; https://doi.org/10.3390/molecules25051229
Received: 15 January 2020 / Revised: 2 March 2020 / Accepted: 6 March 2020 / Published: 9 March 2020
(This article belongs to the Special Issue Bioactive Natural Compounds and Their Mechanisms of Action)
Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules. View Full-Text
Keywords: thyroid cancer; cell proliferation; sanguinarine; cisplatin; STAT3; apoptosis; autophagy thyroid cancer; cell proliferation; sanguinarine; cisplatin; STAT3; apoptosis; autophagy
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Khan, A.Q.; Mohamed, E.A.N.; Hakeem, I.; Nazeer, A.; Kuttikrishnan, S.; Prabhu, K.S.; Siveen, K.S.; Nawaz, Z.; Ahmad, A.; Zayed, H.; Uddin, S. Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species. Molecules 2020, 25, 1229.

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