Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.
Identifieur interne : 000055 ( PubMed/Corpus ); précédent : 000054; suivant : 000056Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.
Auteurs : Hyo In Kim ; Se Hyang Hong ; Jin Mo Ku ; Ye Seul Lim ; Sol Ji Lee ; Jungbin Song ; Tai Young Kim ; Chunhoo Cheon ; Seong-Gyu KoSource :
- The American journal of Chinese medicine [ 1793-6853 ] ; 2019.
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
DOI: 10.1142/S0192415X19500368
PubMed: 30974965
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pubmed:30974965Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.</title><author><name sortKey="Kim, Hyo In" sort="Kim, Hyo In" uniqKey="Kim H" first="Hyo In" last="Kim">Hyo In Kim</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Hong, Se Hyang" sort="Hong, Se Hyang" uniqKey="Hong S" first="Se Hyang" last="Hong">Se Hyang Hong</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Ku, Jin Mo" sort="Ku, Jin Mo" uniqKey="Ku J" first="Jin Mo" last="Ku">Jin Mo Ku</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lim, Ye Seul" sort="Lim, Ye Seul" uniqKey="Lim Y" first="Ye Seul" last="Lim">Ye Seul Lim</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Sol Ji" sort="Lee, Sol Ji" uniqKey="Lee S" first="Sol Ji" last="Lee">Sol Ji Lee</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Song, Jungbin" sort="Song, Jungbin" uniqKey="Song J" first="Jungbin" last="Song">Jungbin Song</name><affiliation><nlm:affiliation>‡ Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Tai Young" sort="Kim, Tai Young" uniqKey="Kim T" first="Tai Young" last="Kim">Tai Young Kim</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Cheon, Chunhoo" sort="Cheon, Chunhoo" uniqKey="Cheon C" first="Chunhoo" last="Cheon">Chunhoo Cheon</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Ko, Seong Gyu" sort="Ko, Seong Gyu" uniqKey="Ko S" first="Seong-Gyu" last="Ko">Seong-Gyu Ko</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30974965</idno><idno type="pmid">30974965</idno><idno type="doi">10.1142/S0192415X19500368</idno><idno type="wicri:Area/PubMed/Corpus">000055</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000055</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.</title><author><name sortKey="Kim, Hyo In" sort="Kim, Hyo In" uniqKey="Kim H" first="Hyo In" last="Kim">Hyo In Kim</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Hong, Se Hyang" sort="Hong, Se Hyang" uniqKey="Hong S" first="Se Hyang" last="Hong">Se Hyang Hong</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Ku, Jin Mo" sort="Ku, Jin Mo" uniqKey="Ku J" first="Jin Mo" last="Ku">Jin Mo Ku</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lim, Ye Seul" sort="Lim, Ye Seul" uniqKey="Lim Y" first="Ye Seul" last="Lim">Ye Seul Lim</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Sol Ji" sort="Lee, Sol Ji" uniqKey="Lee S" first="Sol Ji" last="Lee">Sol Ji Lee</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Song, Jungbin" sort="Song, Jungbin" uniqKey="Song J" first="Jungbin" last="Song">Jungbin Song</name><affiliation><nlm:affiliation>‡ Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Tai Young" sort="Kim, Tai Young" uniqKey="Kim T" first="Tai Young" last="Kim">Tai Young Kim</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Cheon, Chunhoo" sort="Cheon, Chunhoo" uniqKey="Cheon C" first="Chunhoo" last="Cheon">Chunhoo Cheon</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Ko, Seong Gyu" sort="Ko, Seong Gyu" uniqKey="Ko S" first="Seong-Gyu" last="Ko">Seong-Gyu Ko</name><affiliation><nlm:affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The American journal of Chinese medicine</title><idno type="eISSN">1793-6853</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (metabolism)</term><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></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Scutellaria baicalensis</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</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" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Plant Extracts</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Stimulation, Chemical</term><term>Tumor Cells, Cultured</term></keywords></textClass></profileDesc></teiHeader><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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30974965</PMID><DateCompleted><Year>2019</Year><Month>10</Month><Day>17</Day></DateCompleted><DateRevised><Year>2019</Year><Month>10</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1793-6853</ISSN><JournalIssue CitedMedium="Internet"><Volume>47</Volume><Issue>3</Issue><PubDate><Year>2019</Year></PubDate></JournalIssue><Title>The American journal of Chinese medicine</Title><ISOAbbreviation>Am. J. Chin. Med.</ISOAbbreviation></Journal><ArticleTitle>Scutellaria Radix Promotes Apoptosis in Non-Small Cell Lung Cancer Cells via Induction of AMPK-Dependent Autophagy.</ArticleTitle><Pagination><MedlinePgn>691-705</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1142/S0192415X19500368</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Hyo In</ForeName><Initials>HI</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>† Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hong</LastName><ForeName>Se Hyang</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ku</LastName><ForeName>Jin Mo</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lim</LastName><ForeName>Ye Seul</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>† Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Sol Ji</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>† Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Jungbin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>‡ Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Tai Young</ForeName><Initials>TY</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheon</LastName><ForeName>Chunhoo</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ko</LastName><ForeName>Seong-Gyu</ForeName><Initials>SG</Initials><AffiliationInfo><Affiliation>* Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>04</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>Singapore</Country><MedlineTA>Am J Chin Med</MedlineTA><NlmUniqueID>7901431</NlmUniqueID><ISSNLinking>0192-415X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010936">Plant Extracts</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.31</RegistryNumber><NameOfSubstance UI="D055372">AMP-Activated Protein Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D055372" MajorTopicYN="N">AMP-Activated Protein Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002289" MajorTopicYN="N">Carcinoma, Non-Small-Cell Lung</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010936" MajorTopicYN="N">Plant Extracts</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D031364" MajorTopicYN="N">Scutellaria baicalensis</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013268" MajorTopicYN="N">Stimulation, Chemical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">AMP-Activated Protein Kinase</Keyword><Keyword MajorTopicYN="N">Apoptosis</Keyword><Keyword MajorTopicYN="N">Autophagy</Keyword><Keyword MajorTopicYN="N">Non-Small Cell Lung Cancer</Keyword><Keyword MajorTopicYN="N">Scutellaria Radix</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>4</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>10</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>4</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30974965</ArticleId><ArticleId IdType="doi">10.1142/S0192415X19500368</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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