Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.
Identifieur interne : 000438 ( Main/Exploration ); précédent : 000437; suivant : 000439Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.
Auteurs : Hyo In Kim [Corée du Sud] ; Se Hyang Hong [Corée du Sud] ; Jin Mo Ku [Corée du Sud] ; Ye Seul Lim [Corée du Sud] ; Sol Ji Lee [Corée du Sud] ; Jungbin Song [Corée du Sud] ; Tai Young Kim [Corée du Sud] ; Chunhoo Cheon [Corée du Sud] ; Seong-Gyu Ko [Corée du Sud]Source :
- The American journal of Chinese medicine [ 1793-6853 ] ; 2019.
Descripteurs français
- KwdFr :
- AMP-Activated Protein Kinases (métabolisme), Activation chimique, Apoptose (), Autophagie (), Carcinome pulmonaire non à petites cellules (anatomopathologie), Cellules cancéreuses en culture, Extraits de plantes (pharmacologie), Humains, Scutellaria baicalensis (), Tumeurs du poumon (anatomopathologie).
- MESH :
- anatomopathologie : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- métabolisme : AMP-Activated Protein Kinases.
- pharmacologie : Extraits de plantes.
- Activation chimique, Apoptose, Autophagie, Cellules cancéreuses en culture, Humains, Scutellaria baicalensis.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : AMP-Activated Protein Kinases.
- chemistry : Scutellaria baicalensis.
- drug effects : Apoptosis, Autophagy.
- pathology : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- chemical , pharmacology : Plant Extracts.
- Humans, Stimulation, Chemical, Tumor Cells, Cultured.
Abstract
Scutellaria Radix (SR) is an herb traditionally used in Asian countries to treat inflammatory diseases. Recent studies report that SR exhibits anticancer activities in various types of tumors. In this study, we investigated the apoptotic and autophagic effect of SR in non-small cell lung cancer (NSCLC), the leading cause of cancer-associated death. Treatment of SR in two NSCLC cell lines, H358 and H2087 cells resulted in suppressed cell viability. Western blot assays showed increased expressions of Bcl-2-associated X protein (Bax), cleaved-caspase 3 and cleaved-Poly ADP ribose polymerase (PARP), key factors of apoptosis. Co-treatment of SR with a caspase inhibitor Z-VAD led to nullification of the antiproliferative effect, suggesting the role of apoptosis in the action mechanism of SR. Further experiments revealed autophagy was involved in the effect of SR. SR-treated NSCLC cells expressed increased ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I. When chloroquine was co-treated with SR, this ratio was further increased, indicating SR treatment induced autophagy in NSCLC cells. Interestingly, loss of autophagy by 3-Methyladenine (3-MA) co-treatment suppressed SR-induced apoptosis. We then evaluated the relevance of AMP-activated protein kinase (AMPK) in the autophagic/apoptotic process in NSCLC by SR treatment. Immunoblot assays showed increased phosphorylation of AMPK α and P70-S6 kinase in SR-treated H358 and H2087 cells. Under AMPK-inhibited conditions by compound C, SR treatment failed to induce both autophagy and apoptosis. Taken together, this study identifies the positive effect of SR in H358 and H2087 cells by inducing apoptosis via AMPK-dependent autophagy. Thus, our results suggest the potential use of SR as a novel therapeutic strategy for NSCLC patients.
DOI: 10.1142/S0192415X19500368
PubMed: 30974965
Affiliations:
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<term>Apoptosis (drug effects)</term>
<term>Autophagy (drug effects)</term>
<term>Carcinoma, Non-Small-Cell Lung (pathology)</term>
<term>Humans</term>
<term>Lung Neoplasms (pathology)</term>
<term>Plant Extracts (pharmacology)</term>
<term>Scutellaria baicalensis (chemistry)</term>
<term>Stimulation, Chemical</term>
<term>Tumor Cells, Cultured</term>
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<term>Activation chimique</term>
<term>Apoptose ()</term>
<term>Autophagie ()</term>
<term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term>
<term>Cellules cancéreuses en culture</term>
<term>Extraits de plantes (pharmacologie)</term>
<term>Humains</term>
<term>Scutellaria baicalensis ()</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
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<term>Tumeurs du poumon</term>
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<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Scutellaria baicalensis</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term>
<term>Autophagy</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Extraits de plantes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Plant Extracts</term>
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<term>Tumor Cells, Cultured</term>
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<term>Apoptose</term>
<term>Autophagie</term>
<term>Cellules cancéreuses en culture</term>
<term>Humains</term>
<term>Scutellaria baicalensis</term>
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<front><div type="abstract" xml:lang="en">Scutellaria Radix (SR) is an herb traditionally used in Asian countries to treat inflammatory diseases. Recent studies report that SR exhibits anticancer activities in various types of tumors. In this study, we investigated the apoptotic and autophagic effect of SR in non-small cell lung cancer (NSCLC), the leading cause of cancer-associated death. Treatment of SR in two NSCLC cell lines, H358 and H2087 cells resulted in suppressed cell viability. Western blot assays showed increased expressions of Bcl-2-associated X protein (Bax), cleaved-caspase 3 and cleaved-Poly ADP ribose polymerase (PARP), key factors of apoptosis. Co-treatment of SR with a caspase inhibitor Z-VAD led to nullification of the antiproliferative effect, suggesting the role of apoptosis in the action mechanism of SR. Further experiments revealed autophagy was involved in the effect of SR. SR-treated NSCLC cells expressed increased ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I. When chloroquine was co-treated with SR, this ratio was further increased, indicating SR treatment induced autophagy in NSCLC cells. Interestingly, loss of autophagy by 3-Methyladenine (3-MA) co-treatment suppressed SR-induced apoptosis. We then evaluated the relevance of AMP-activated protein kinase (AMPK) in the autophagic/apoptotic process in NSCLC by SR treatment. Immunoblot assays showed increased phosphorylation of AMPK <mml:math><mml:mi>α</mml:mi>
</mml:math>
and P70-S6 kinase in SR-treated H358 and H2087 cells. Under AMPK-inhibited conditions by compound C, SR treatment failed to induce both autophagy and apoptosis. Taken together, this study identifies the positive effect of SR in H358 and H2087 cells by inducing apoptosis via AMPK-dependent autophagy. Thus, our results suggest the potential use of SR as a novel therapeutic strategy for NSCLC patients.</div>
</front>
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<name sortKey="Kim, Tai Young" sort="Kim, Tai Young" uniqKey="Kim T" first="Tai Young" last="Kim">Tai Young Kim</name>
<name sortKey="Ko, Seong Gyu" sort="Ko, Seong Gyu" uniqKey="Ko S" first="Seong-Gyu" last="Ko">Seong-Gyu Ko</name>
<name sortKey="Ku, Jin Mo" sort="Ku, Jin Mo" uniqKey="Ku J" first="Jin Mo" last="Ku">Jin Mo Ku</name>
<name sortKey="Lee, Sol Ji" sort="Lee, Sol Ji" uniqKey="Lee S" first="Sol Ji" last="Lee">Sol Ji Lee</name>
<name sortKey="Lim, Ye Seul" sort="Lim, Ye Seul" uniqKey="Lim Y" first="Ye Seul" last="Lim">Ye Seul Lim</name>
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