Next Article in Journal
Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells
Next Article in Special Issue
Protective Effects of Zerumbone on Colonic Tumorigenesis in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized AOM/DSS BALB/c Mice
Previous Article in Journal
Preferential Coupling of Dopamine D2S and D2L Receptor Isoforms with Gi1 and Gi2 Proteins—In Silico Study
Previous Article in Special Issue
Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma
Article

Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

1
Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar
2
National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar
3
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA
4
Department of Dermatology and Venereology, Hamad Medical Corporation, Doha 3050, Qatar
5
Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, Doha 24144, Qatar
6
Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
7
College of Medicine, Qatar University, Doha 2713, Qatar
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 438; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020438
Received: 12 December 2019 / Revised: 31 December 2019 / Accepted: 6 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue The Effect of Dietary Factors on Cancer 2.0)
The constitutive activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signal transduction is well elucidated in STAT3-mediated oncogenesis related to thyroid cancer and is considered to be a plausible therapeutic target. Hence, we investigated whether curcumin, a natural compound, can target the JAK/STAT3 signaling pathway to induce cytotoxic effects in papillary thyroid cancer (PTC) cell lines (BCPAP and TPC-1) and derived thyroid cancer stem-like cells (thyrospheres). Curcumin suppressed PTC cell survival in a dose-dependent manner via the induction of caspase-mediated apoptosis and caused the attenuation of constitutively active STAT3 (the dephosphorylation of Tyr705–STAT3) without affecting STAT3. Gene silencing with STAT3-specific siRNA showed the modulation of genes associated with cell growth and proliferation. The cotreatment of PTC cell lines with curcumin and cisplatin synergistically potentiated cytotoxic effects via the suppression of JAK/STAT3 activity along with the inhibition of antiapoptotic genes and the induction of proapoptotic genes, and it also suppressed the migration of PTC cells by downregulating matrix metalloproteinases and the inhibition of colony formation. Finally, thyrospheres treated with curcumin and cisplatin showed suppressed STAT3 phosphorylation, a reduced formation of thyrospheres, and the downregulated expression of stemness markers, in addition to apoptosis. The current study’s findings suggest that curcumin synergistically enhances the anticancer activity of cisplatin in PTC cells as well as in cancer stem-like cells by targeting STAT3, which suggests that curcumin combined with chemotherapeutic agents may provide better therapeutic outcomes. View Full-Text
Keywords: thyroid cancer; curcumin; cisplatin; STAT3; cell proliferation; cancer stem cells; apoptosis thyroid cancer; curcumin; cisplatin; STAT3; cell proliferation; cancer stem cells; apoptosis
Show Figures

Figure 1

MDPI and ACS Style

Khan, A.Q.; Ahmed, E.I.; Elareer, N.; Fathima, H.; Prabhu, K.S.; Siveen, K.S.; Kulinski, M.; Azizi, F.; Dermime, S.; Ahmad, A.; Steinhoff, M.; Uddin, S. Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway. Int. J. Mol. Sci. 2020, 21, 438. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020438

AMA Style

Khan AQ, Ahmed EI, Elareer N, Fathima H, Prabhu KS, Siveen KS, Kulinski M, Azizi F, Dermime S, Ahmad A, Steinhoff M, Uddin S. Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway. International Journal of Molecular Sciences. 2020; 21(2):438. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020438

Chicago/Turabian Style

Khan, Abdul Q., Eiman I. Ahmed, Noor Elareer, Hamna Fathima, Kirti S. Prabhu, Kodappully S. Siveen, Michal Kulinski, Fouad Azizi, Said Dermime, Aamir Ahmad, Martin Steinhoff, and Shahab Uddin. 2020. "Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway" International Journal of Molecular Sciences 21, no. 2: 438. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020438

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop