Next Article in Journal
Long Non Coding RNA H19: A New Player in Hypoxia-Induced Multiple Myeloma Cell Dissemination
Next Article in Special Issue
Phenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells
Previous Article in Journal
Grain Legumes and Fear of Salt Stress: Focus on Mechanisms and Management Strategies
Previous Article in Special Issue
Potent Anti-Cancer Properties of Phthalimide-Based Curcumin Derivatives on Prostate Tumor Cells
Article Menu
Issue 4 (February-2) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2019, 20(4), 800; https://doi.org/10.3390/ijms20040800

Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs

1
College of Basic Sciences, King Faisal University, Hofuf, 400, Al Ahsa 31982, Saudi Arabia
2
Clinical Biochemistry, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
3
Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk 71491, Saudi Arabia
4
Department of Psychiatry, University Hospital Limerick, Limerick V94 T9PX, Ireland
5
Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan
6
Organic Chemistry Laboratory, Universitätsstr. 30, 95447 Bayreuth, Germany
7
Department of Pathology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA
*
Author to whom correspondence should be addressed.
Present Address: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Received: 19 December 2018 / Revised: 7 February 2019 / Accepted: 11 February 2019 / Published: 13 February 2019
(This article belongs to the Special Issue The Effect of Dietary Factors on Cancer)
Full-Text   |   PDF [1262 KB, uploaded 13 February 2019]   |  

Abstract

Garcinol, a dietary factor obtained from Garcinia indica, modulates several key cellular signaling pathways as well as the expression of miRNAs. Acquired resistance to standard therapies, such as erlotinib and cisplatin, is a hallmark of non-small cell lung cancer (NSCLC) cells that often involves miRNA-regulated epithelial-to-mesenchymal transition (EMT). We used A549 cells that were exposed to transforming growth factor beta 1 (TGF-β1), resulting in A549M cells with mesenchymal and drug resistant phenotype, and report that garcinol sensitized resistant cells with mesenchymal phenotype to erlotinib as well as cisplatin with significant decrease in their IC50 values. It also potentiated the apoptosis-inducing activity of erlotinib in A549M and the endogenously mesenchymal H1299 NSCLC cells. Further, garcinol significantly upregulated several key EMT-regulating miRNAs, such as miR-200b, miR-205, miR-218, and let-7c. Antagonizing miRNAs, through anti-miRNA transfections, attenuated the EMT-modulating activity of garcinol, as determined by mRNA expression of EMT markers, E-cadherin, vimentin, and Zinc Finger E-Box Binding Homeobox 1 (ZEB1). This further led to repression of erlotinib as well as cisplatin sensitization, thus establishing the mechanistic role of miRNAs, particularly miR-200c and let-7c, in garcinol-mediated reversal of EMT and the resulting sensitization of NSCLC cells to standard therapies. View Full-Text
Keywords: garcinol; NSCLC; EMT; erlotinib; cisplatin; miRNAs garcinol; NSCLC; EMT; erlotinib; cisplatin; miRNAs
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Farhan, M.; Malik, A.; Ullah, M.F.; Afaq, S.; Faisal, M.; Farooqi, A.A.; Biersack, B.; Schobert, R.; Ahmad, A. Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs. Int. J. Mol. Sci. 2019, 20, 800.

Show more citation formats Show less citations formats

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

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top