Cargando…

Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma

Natural medicinal plants are multi-targeted in nature and their anti-cancer activities are also complex and varied, thus requiring a more systematic analysis of their modes of action. Since the activation of signal transducer and activator of transcription 3 (STAT3) is often deregulated in non-small...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Jong Hyun, Kim, Chulwon, Lee, Seok-Geun, Sethi, Gautam, Ahn, Kwang Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265752/
https://www.ncbi.nlm.nih.gov/pubmed/30413072
http://dx.doi.org/10.3390/cancers10110427
_version_ 1783375690619420672
author Lee, Jong Hyun
Kim, Chulwon
Lee, Seok-Geun
Sethi, Gautam
Ahn, Kwang Seok
author_facet Lee, Jong Hyun
Kim, Chulwon
Lee, Seok-Geun
Sethi, Gautam
Ahn, Kwang Seok
author_sort Lee, Jong Hyun
collection PubMed
description Natural medicinal plants are multi-targeted in nature and their anti-cancer activities are also complex and varied, thus requiring a more systematic analysis of their modes of action. Since the activation of signal transducer and activator of transcription 3 (STAT3) is often deregulated in non-small cell lung carcinoma (NSCLC) cells and tissue specimens, its negative regulation can form the basis for identification of targeted therapy. In this report, we analyzed the possible anti-cancer effects of ophiopogonin D (OP-D) and the underlying mechanisms by which OP-D exerts its actions in NSCLC. OP-D exhibited substantial suppressive activity on STAT3 signaling and this effect was found to be mediated via oxidative stress phenomena caused by disturbance in GSH/GSSG ratio. In addition, OP-D induced apoptosis, activated caspase mediated apoptotic cascade and decreased expression of various oncogenic genes. Consistently, OP-D treatment significantly reduced NSCLC tumor growth in preclinical mouse model with via decreasing levels of p-STAT3. OP-D was also found to attenuate the expression of STAT3-regulated anti-apoptosis, cell cycle regulator, and angiogenesis biomarkers. Our findings suggest that OP-D can induce apoptosis and exert anti-tumor effects by inhibition of STAT3 signaling pathways in NSCLC.
format Online
Article
Text
id pubmed-6265752
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62657522018-12-03 Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma Lee, Jong Hyun Kim, Chulwon Lee, Seok-Geun Sethi, Gautam Ahn, Kwang Seok Cancers (Basel) Article Natural medicinal plants are multi-targeted in nature and their anti-cancer activities are also complex and varied, thus requiring a more systematic analysis of their modes of action. Since the activation of signal transducer and activator of transcription 3 (STAT3) is often deregulated in non-small cell lung carcinoma (NSCLC) cells and tissue specimens, its negative regulation can form the basis for identification of targeted therapy. In this report, we analyzed the possible anti-cancer effects of ophiopogonin D (OP-D) and the underlying mechanisms by which OP-D exerts its actions in NSCLC. OP-D exhibited substantial suppressive activity on STAT3 signaling and this effect was found to be mediated via oxidative stress phenomena caused by disturbance in GSH/GSSG ratio. In addition, OP-D induced apoptosis, activated caspase mediated apoptotic cascade and decreased expression of various oncogenic genes. Consistently, OP-D treatment significantly reduced NSCLC tumor growth in preclinical mouse model with via decreasing levels of p-STAT3. OP-D was also found to attenuate the expression of STAT3-regulated anti-apoptosis, cell cycle regulator, and angiogenesis biomarkers. Our findings suggest that OP-D can induce apoptosis and exert anti-tumor effects by inhibition of STAT3 signaling pathways in NSCLC. MDPI 2018-11-08 /pmc/articles/PMC6265752/ /pubmed/30413072 http://dx.doi.org/10.3390/cancers10110427 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Jong Hyun
Kim, Chulwon
Lee, Seok-Geun
Sethi, Gautam
Ahn, Kwang Seok
Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma
title Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma
title_full Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma
title_fullStr Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma
title_full_unstemmed Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma
title_short Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma
title_sort ophiopogonin d, a steroidal glycoside abrogates stat3 signaling cascade and exhibits anti-cancer activity by causing gsh/gssg imbalance in lung carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265752/
https://www.ncbi.nlm.nih.gov/pubmed/30413072
http://dx.doi.org/10.3390/cancers10110427
work_keys_str_mv AT leejonghyun ophiopogonindasteroidalglycosideabrogatesstat3signalingcascadeandexhibitsanticanceractivitybycausinggshgssgimbalanceinlungcarcinoma
AT kimchulwon ophiopogonindasteroidalglycosideabrogatesstat3signalingcascadeandexhibitsanticanceractivitybycausinggshgssgimbalanceinlungcarcinoma
AT leeseokgeun ophiopogonindasteroidalglycosideabrogatesstat3signalingcascadeandexhibitsanticanceractivitybycausinggshgssgimbalanceinlungcarcinoma
AT sethigautam ophiopogonindasteroidalglycosideabrogatesstat3signalingcascadeandexhibitsanticanceractivitybycausinggshgssgimbalanceinlungcarcinoma
AT ahnkwangseok ophiopogonindasteroidalglycosideabrogatesstat3signalingcascadeandexhibitsanticanceractivitybycausinggshgssgimbalanceinlungcarcinoma