PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Docosahexaenoic Acid Induces Cell Death through Downregulation of Hedgehog Signaling via Surt6 Activation in Human EGFR Mutant Non-Small Cell Lung Cancer
Version 1
: Received: 20 October 2017 / Approved: 24 October 2017 / Online: 24 October 2017 (05:43:16 CEST)
How to cite:
Jeong, S.; Jing, K.; Shin, S.; Kim, S.; Han, S.-H.; Yoo, Y.-S.; Jeon, Y.-J.; Heo, J.-Y.; Kweon, G.-R.; Park, S.-K.; Park, J.-I.; Lim, K. Docosahexaenoic Acid Induces Cell Death through Downregulation of Hedgehog Signaling via Surt6 Activation in Human EGFR Mutant Non-Small Cell Lung Cancer. Preprints2017, 2017100157. https://doi.org/10.20944/preprints201710.0157.v1
Jeong, S.; Jing, K.; Shin, S.; Kim, S.; Han, S.-H.; Yoo, Y.-S.; Jeon, Y.-J.; Heo, J.-Y.; Kweon, G.-R.; Park, S.-K.; Park, J.-I.; Lim, K. Docosahexaenoic Acid Induces Cell Death through Downregulation of Hedgehog Signaling via Surt6 Activation in Human EGFR Mutant Non-Small Cell Lung Cancer. Preprints 2017, 2017100157. https://doi.org/10.20944/preprints201710.0157.v1
Jeong, S.; Jing, K.; Shin, S.; Kim, S.; Han, S.-H.; Yoo, Y.-S.; Jeon, Y.-J.; Heo, J.-Y.; Kweon, G.-R.; Park, S.-K.; Park, J.-I.; Lim, K. Docosahexaenoic Acid Induces Cell Death through Downregulation of Hedgehog Signaling via Surt6 Activation in Human EGFR Mutant Non-Small Cell Lung Cancer. Preprints2017, 2017100157. https://doi.org/10.20944/preprints201710.0157.v1
APA Style
Jeong, S., Jing, K., Shin, S., Kim, S., Han, S. H., Yoo, Y. S., Jeon, Y. J., Heo, J. Y., Kweon, G. R., Park, S. K., Park, J. I., & Lim, K. (2017). Docosahexaenoic Acid Induces Cell Death through Downregulation of Hedgehog Signaling via Surt6 Activation in Human EGFR Mutant Non-Small Cell Lung Cancer. Preprints. https://doi.org/10.20944/preprints201710.0157.v1
Chicago/Turabian Style
Jeong, S., Jong-Il Park and Kyu Lim. 2017 "Docosahexaenoic Acid Induces Cell Death through Downregulation of Hedgehog Signaling via Surt6 Activation in Human EGFR Mutant Non-Small Cell Lung Cancer" Preprints. https://doi.org/10.20944/preprints201710.0157.v1
Abstract
Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
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.