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Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway

Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further i...

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Autores principales: Kim, Sang-A, Kang, Ok-Hwa, Kwon, Dong-Yeul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163873/
https://www.ncbi.nlm.nih.gov/pubmed/30217003
http://dx.doi.org/10.3390/ijms19092739
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author Kim, Sang-A
Kang, Ok-Hwa
Kwon, Dong-Yeul
author_facet Kim, Sang-A
Kang, Ok-Hwa
Kwon, Dong-Yeul
author_sort Kim, Sang-A
collection PubMed
description Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further investigated the anti-cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated with CTT reduced cell growth through PI3K/Akt/GSK3β pathway inhibition, G0/G1 cell cycle arrest, and the activation of apoptosis. CTT induced an increase of caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and 2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These results highlight anti-proliferation the latent of CTT as natural therapeutic agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti-cancer agent by comparing with GF, which is a representative anti-cancer drug.
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spelling pubmed-61638732018-10-10 Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway Kim, Sang-A Kang, Ok-Hwa Kwon, Dong-Yeul Int J Mol Sci Article Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further investigated the anti-cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated with CTT reduced cell growth through PI3K/Akt/GSK3β pathway inhibition, G0/G1 cell cycle arrest, and the activation of apoptosis. CTT induced an increase of caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and 2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These results highlight anti-proliferation the latent of CTT as natural therapeutic agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti-cancer agent by comparing with GF, which is a representative anti-cancer drug. MDPI 2018-09-13 /pmc/articles/PMC6163873/ /pubmed/30217003 http://dx.doi.org/10.3390/ijms19092739 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
Kim, Sang-A
Kang, Ok-Hwa
Kwon, Dong-Yeul
Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
title Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
title_full Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
title_fullStr Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
title_full_unstemmed Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
title_short Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
title_sort cryptotanshinone induces cell cycle arrest and apoptosis of nsclc cells through the pi3k/akt/gsk-3β pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163873/
https://www.ncbi.nlm.nih.gov/pubmed/30217003
http://dx.doi.org/10.3390/ijms19092739
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