Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes
Identifieur interne : 000219 ( Pmc/Checkpoint ); précédent : 000218; suivant : 000220Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes
Auteurs : Hyo In Kim ; Se Hyang Hong ; Jin Mo Ku ; Min Jeong Kim ; Sung Wan Ju ; Seok Won Chang ; Chunhoo Cheon ; Seong-Gyu KoSource :
- Nutrients [ 2072-6643 ] ; 2020.
Abstract
Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required.
Url:
DOI: 10.3390/nu12010196
PubMed: 31936835
PubMed Central: 7019269
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>Gardenia jasminoides</italic> Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes</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:aff id="af1-nutrients-12-00196">Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</nlm:aff></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:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></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:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Min Jeong" sort="Kim, Min Jeong" uniqKey="Kim M" first="Min Jeong" last="Kim">Min Jeong Kim</name><affiliation><nlm:aff id="af1-nutrients-12-00196">Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</nlm:aff></affiliation></author><author><name sortKey="Ju, Sung Wan" sort="Ju, Sung Wan" uniqKey="Ju S" first="Sung Wan" last="Ju">Sung Wan Ju</name><affiliation><nlm:aff id="af1-nutrients-12-00196">Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</nlm:aff></affiliation></author><author><name sortKey="Chang, Seok Won" sort="Chang, Seok Won" uniqKey="Chang S" first="Seok Won" last="Chang">Seok Won Chang</name><affiliation><nlm:aff id="af3-nutrients-12-00196">Department of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>jsw2333@hanmail.net</email></nlm:aff></affiliation></author><author><name sortKey="Cheon, Chunhoo" sort="Cheon, Chunhoo" uniqKey="Cheon C" first="Chunhoo" last="Cheon">Chunhoo Cheon</name><affiliation><nlm:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></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:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31936835</idno><idno type="pmc">7019269</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019269</idno><idno type="RBID">PMC:7019269</idno><idno type="doi">10.3390/nu12010196</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000735</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000735</idno><idno type="wicri:Area/Pmc/Curation">000735</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000735</idno><idno type="wicri:Area/Pmc/Checkpoint">000219</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000219</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Gardenia jasminoides</italic> Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes</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:aff id="af1-nutrients-12-00196">Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</nlm:aff></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:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></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:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Min Jeong" sort="Kim, Min Jeong" uniqKey="Kim M" first="Min Jeong" last="Kim">Min Jeong Kim</name><affiliation><nlm:aff id="af1-nutrients-12-00196">Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</nlm:aff></affiliation></author><author><name sortKey="Ju, Sung Wan" sort="Ju, Sung Wan" uniqKey="Ju S" first="Sung Wan" last="Ju">Sung Wan Ju</name><affiliation><nlm:aff id="af1-nutrients-12-00196">Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</nlm:aff></affiliation></author><author><name sortKey="Chang, Seok Won" sort="Chang, Seok Won" uniqKey="Chang S" first="Seok Won" last="Chang">Seok Won Chang</name><affiliation><nlm:aff id="af3-nutrients-12-00196">Department of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>jsw2333@hanmail.net</email></nlm:aff></affiliation></author><author><name sortKey="Cheon, Chunhoo" sort="Cheon, Chunhoo" uniqKey="Cheon C" first="Chunhoo" last="Cheon">Chunhoo Cheon</name><affiliation><nlm:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></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:aff id="af2-nutrients-12-00196">Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</nlm:aff></affiliation></author></analytic><series><title level="j">Nutrients</title><idno type="eISSN">2072-6643</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. <italic>Gardenia jasminoides</italic> (GJ) is flavonoid abundant with beneficial effects on inflammation, metabolic diseases, and cancers. In this study, we investigated the synergistic combination of GJ and cisplatin (CDDP) in U87MG and U373MG GBM cells. GJ and CDDP both showed cytotoxicity in U87MG cells, however GJ did not affect viability of normal astrocytes while CDDP displayed high toxicity. Cytotoxic effect of GJ and CDDP was related in apoptosis when confirmed by Western blot assays on cleaved caspase-3, caspase-9, and PARP. Moreover, GJ and CDDP showed synergistic combination in cell death of GBM cells, which was further confirmed by Western blot assays of apoptosis factors and also flow cytometry of Annexin V. Analysis on autophagy factors showed that GJ/CDDP combination induced autophagy, and through inhibition of autophagy, we could confirm autophagy is crucial to cytotoxicity of GJ/CDDP in GBM cell lines. The autophagy-mediated apoptosis of GJ/CDDP was dependent on the AKT/mTOR pathway. Overall, our results suggest GJ/CDDP combination as an effective yet safe therapeutic approach to GBMs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ostrom, Q T" uniqKey="Ostrom Q">Q.T. Ostrom</name></author><author><name sortKey="Gittleman, H" uniqKey="Gittleman H">H. Gittleman</name></author><author><name sortKey="Truitt, G" uniqKey="Truitt G">G. Truitt</name></author><author><name sortKey="Boscia, A" uniqKey="Boscia A">A. Boscia</name></author><author><name sortKey="Kruchko, C" uniqKey="Kruchko C">C. Kruchko</name></author><author><name sortKey="Barnholtz Sloan, J S" uniqKey="Barnholtz Sloan J">J.S. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nutrients</journal-id><journal-id journal-id-type="iso-abbrev">Nutrients</journal-id><journal-id journal-id-type="publisher-id">nutrients</journal-id><journal-title-group><journal-title>Nutrients</journal-title></journal-title-group><issn pub-type="epub">2072-6643</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31936835</article-id><article-id pub-id-type="pmc">7019269</article-id><article-id pub-id-type="doi">10.3390/nu12010196</article-id><article-id pub-id-type="publisher-id">nutrients-12-00196</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title><italic>Gardenia jasminoides</italic> Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Hyo In</given-names></name><xref ref-type="aff" rid="af1-nutrients-12-00196">1</xref></contrib><contrib contrib-type="author"><name><surname>Hong</surname><given-names>Se Hyang</given-names></name><xref ref-type="aff" rid="af2-nutrients-12-00196">2</xref></contrib><contrib contrib-type="author"><name><surname>Ku</surname><given-names>Jin Mo</given-names></name><xref ref-type="aff" rid="af2-nutrients-12-00196">2</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Min Jeong</given-names></name><xref ref-type="aff" rid="af1-nutrients-12-00196">1</xref></contrib><contrib contrib-type="author"><name><surname>Ju</surname><given-names>Sung Wan</given-names></name><xref ref-type="aff" rid="af1-nutrients-12-00196">1</xref></contrib><contrib contrib-type="author"><name><surname>Chang</surname><given-names>Seok Won</given-names></name><xref ref-type="aff" rid="af3-nutrients-12-00196">3</xref></contrib><contrib contrib-type="author"><name><surname>Cheon</surname><given-names>Chunhoo</given-names></name><xref ref-type="aff" rid="af2-nutrients-12-00196">2</xref><xref rid="c1-nutrients-12-00196" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Ko</surname><given-names>Seong-Gyu</given-names></name><xref ref-type="aff" rid="af2-nutrients-12-00196">2</xref><xref rid="c1-nutrients-12-00196" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-nutrients-12-00196"><label>1</label>Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>hi9265@nate.com</email> (H.I.K.);<email>jung8328@hanmail.net</email> (M.J.K.);<email>seonca@naver.com</email> (S.W.J.)</aff><aff id="af2-nutrients-12-00196"><label>2</label>Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>sehyang@khu.ac.kr</email> (S.H.H.);<email>saory_ykm@naver.com</email> (J.M.K.)</aff><aff id="af3-nutrients-12-00196"><label>3</label>Department of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;<email>jsw2333@hanmail.net</email></aff><author-notes><corresp id="c1-nutrients-12-00196"><label>*</label>Correspondence: <email>pm.thehoo@gmail.com</email> (C.C.); <email>epiko@khu.ac.kr</email> (S.-G.K.); Tel.: +82-2-961-9278 (C.C.); +82-2-961-0329 (S.-G.K.); Fax: +82-2-966-1165 (C.C. & S.-G.K.)</corresp></author-notes><pub-date pub-type="epub"><day>10</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>1</month><year>2020</year></pub-date><volume>12</volume><issue>1</issue><elocation-id>196</elocation-id><history><date date-type="received"><day>24</day><month>12</month><year>2019</year></date><date date-type="accepted"><day>07</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>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 (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. <italic>Gardenia jasminoides</italic> (GJ) is flavonoid abundant with beneficial effects on inflammation, metabolic diseases, and cancers. In this study, we investigated the synergistic combination of GJ and cisplatin (CDDP) in U87MG and U373MG GBM cells. GJ and CDDP both showed cytotoxicity in U87MG cells, however GJ did not affect viability of normal astrocytes while CDDP displayed high toxicity. Cytotoxic effect of GJ and CDDP was related in apoptosis when confirmed by Western blot assays on cleaved caspase-3, caspase-9, and PARP. Moreover, GJ and CDDP showed synergistic combination in cell death of GBM cells, which was further confirmed by Western blot assays of apoptosis factors and also flow cytometry of Annexin V. Analysis on autophagy factors showed that GJ/CDDP combination induced autophagy, and through inhibition of autophagy, we could confirm autophagy is crucial to cytotoxicity of GJ/CDDP in GBM cell lines. The autophagy-mediated apoptosis of GJ/CDDP was dependent on the AKT/mTOR pathway. Overall, our results suggest GJ/CDDP combination as an effective yet safe therapeutic approach to GBMs.</p></abstract><kwd-group><kwd>glioblastoma</kwd><kwd><italic>Gardenia jasminoides</italic></kwd><kwd>cisplatin (CDDP)</kwd><kwd>synergy</kwd><kwd>apoptosis</kwd><kwd>autophagy</kwd><kwd>AKT/mTOR pathway</kwd></kwd-group></article-meta></front><floats-group><fig id="nutrients-12-00196-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Effect of GJ and CDDP on cell viability of U87MG and U373MG cells. MTT assays were performed in (<bold>a</bold>) GJ-treated and (<bold>b</bold>) CDDP-treated U87MG cells. (<bold>c</bold>) Microscopical observation of cell morphology was performed in GJ- and CDDP-treated U87MG cells. (<bold>d</bold>) Western blot assays on cleaved caspase-3, cleaved caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) were performed in GJ- and CDDP-treated U87MG cells. MTT assays were performed in (<bold>e</bold>) GJ-treated and (<bold>f</bold>) CDDP-treated U373MG cells. (<bold>g</bold>) Microscopical observation of cell morphology was performed in GJ- and CDDP-treated U373MG cells. Results are displayed as mean ± S.E. of three or more separate experiments. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as endogenous control. * <italic>p</italic> < 0.05 vs. untreated cells, ** <italic>p</italic> < 0.01 vs. untreated cells, *** <italic>p</italic> < 0.005 vs. untreated cells. GJ, <italic>Gardenia jasminoides</italic>; CDDP, cisplatin.</p></caption><graphic xlink:href="nutrients-12-00196-g001"></graphic></fig><fig id="nutrients-12-00196-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Synergistic evaluation of GJ/CDDP combination on cytotoxicity in U87MG and U373MG cells. (<bold>a</bold>) Combination index (CI) (left) and logarithmic CI (right) of GJ/CDDP combination was evaluated. (<bold>b</bold>) An MTT assay was performed to compare the cell viability in GJ-, CDDP-, and GJ/CDDP-treated U87MG cells. (<bold>c</bold>) Microscopic observation of cell morphology in GJ/CDDP combination-treated U87MG cells was performed. (<bold>d</bold>) Crystal violet staining was performed in GJ/CDDP combination-treated U87MG cells. (<bold>e</bold>) An MTT assay was performed to compare the cell viability in GJ-, CDDP-, and GJ/CDDP-treated U373MG cells. (<bold>f</bold>) Microscopic observation of cell morphology in GJ/CDDP combination-treated U373MG cells was performed. (<bold>g</bold>) Crystal violet staining was performed in GJ/CDDP combination-treated U373MG cells. Results are displayed as mean ± S.E. of three or more separate experiments. * <italic>p</italic> < 0.05 vs. untreated cells, ** <italic>p</italic> < 0.01 vs. untreated cells, *** <italic>p</italic> < 0.005 vs. untreated cells. GJ, <italic>Gardenia jasminoides</italic>; CDDP, cisplatin.</p></caption><graphic xlink:href="nutrients-12-00196-g002a"></graphic><graphic xlink:href="nutrients-12-00196-g002b"></graphic></fig><fig id="nutrients-12-00196-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Effect of GJ/CDDP combination on apoptosis factors in U87MG and U373MG cells. (<bold>a</bold>) Western blot assays on cleaved caspase-3, cleaved caspase-9, and cleaved PARP were performed in GJ/CDDP combination-treated U87MG cells. (<bold>b</bold>) Annexin V assay was performed in GJ/CDDP combination-treated U87MG cells. (<bold>c</bold>) An MTT assay was performed in GJ/CDDP combination-treated U87MG cells after pre-treatment with Z-VAD-FMK. (<bold>d</bold>) Western blot assays on cleaved caspase-3, cleaved caspase-9, and cleaved PARP were performed in GJ/CDDP combination-treated U373MG cells. (<bold>e</bold>,<bold>f</bold>) An MTT assay was performed in GJ/CDDP combination-treated U373MG cells after pre-treatment with Z-VAD-FMK. Results are displayed as mean ± S.E. of three or more separate experiments. GAPDH was used as endogenous control. *** <italic>p</italic> < 0.005 vs. untreated cells. GJ, <italic>Gardenia jasminoides</italic>; CDDP, cisplatin.</p></caption><graphic xlink:href="nutrients-12-00196-g003"></graphic></fig><fig id="nutrients-12-00196-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Effect of GJ/CDDP combination on autophagy factors in U87MG and U373MG cells. (<bold>a</bold>) Western blot assays on p672 and microtubule-associated protein 1A/1B-light chain 3 (LC3B)-I/II were performed in GJ- and CDDP-treated U87MG cells. (<bold>b</bold>) Time-dependent change of LC3B-I/II in GJ- and CDDP-treated U87MG cells were measured by Western blot assays. (<bold>c</bold>) Effect of GJ/CDDP combination on p62 and LC3B-I/II was compared to GJ and CDDP single treatment by Western blot assays. (<bold>d</bold>) Western blot assays on p62 and LC3B-I/II were performed in GJ- and CDDP-treated U373MG cells. GAPDH was used as endogenous control. GJ, <italic>Gardenia jasminoides</italic>; CDDP, cisplatin.</p></caption><graphic xlink:href="nutrients-12-00196-g004"></graphic></fig><fig id="nutrients-12-00196-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Effect of GJ/CDDP combination under autophagy-inhibited conditions in U87MG and U373MG cells. (<bold>a</bold>) A Western blot assay on LC3B-I/II and (<bold>b</bold>) an MTT assay was performed in GJ/CDDP combination-treated U87MG cells after pre-treatment with 3-MA. (<bold>c</bold>) A Western blot assay on LC3B-I/II and (<bold>d</bold>) an MTT assay was performed in GJ/CDDP combination-treated U87MG cells after pre-treatment with CQ. (<bold>e</bold>) A Western blot assay on LC3B-I/II and (<bold>f</bold>) an MTT assay was performed in GJ/CDDP combination-treated U373MG cells after pre-treatment with 3-MA. (<bold>g</bold>) A Western blot assay on LC3B-I/II and (<bold>h</bold>) an MTT assay was performed in GJ/CDDP combination-treated U373MG cells after pre-treatment with CQ. Results are displayed as mean ± S.E. of three or more separate experiments. GAPDH was used as endogenous control. *** <italic>p</italic> < 0.005 vs. untreated cells. GJ, <italic>Gardenia jasminoides</italic>; CDDP, cisplatin.</p></caption><graphic xlink:href="nutrients-12-00196-g005"></graphic></fig><fig id="nutrients-12-00196-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Effect of GJ/CDDP combination on AKT/mTOR pathway in U87MG and U373MG cells. Western blot assays on (<bold>a</bold>) p53, (<bold>b</bold>) p-AKT, and (<bold>c</bold>) p-p70S6K were performed in GJ/CDDP combination-treated U87MG cells. (<bold>d</bold>) Western blot assays on p-AKT and LC3B-I/II, and (<bold>e</bold>) an MTT assay were performed in GJ/CDDP combination-treated U87MG cells after pre-treatment with LY294002. (<bold>f</bold>) Western blot assays on p-AKT and LC3B-I/II, and (<bold>g</bold>) an MTT assay was performed in GJ/CDDP combination-treated U87MG cells after pre-treatment with SC79. (<bold>h</bold>) Western blot assays on p53, p-AKT, and p-p70S6K were performed in GJ/CDDP combination-treated U373MG cells. (<bold>i</bold>) Western blot assays on p-AKT and LC3B-I/II were performed in GJ/CDDP combination-treated U373MG cells after pre-treatment with LY294002. (<bold>j</bold>) Western blot assays on p-AKT and LC3B-I/II were performed in GJ/CDDP combination-treated U373MG cells after pre-treatment with SC79. Results are displayed as mean ± S.E. of three or more separate experiments. GAPDH was used as endogenous control. *** <italic>p</italic> < 0.005 vs. untreated cells. GJ, <italic>Gardenia jasminoides</italic>; CDDP, cisplatin.</p></caption><graphic xlink:href="nutrients-12-00196-g006a"></graphic><graphic xlink:href="nutrients-12-00196-g006b"></graphic></fig></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Chang, Seok Won" sort="Chang, Seok Won" uniqKey="Chang S" first="Seok Won" last="Chang">Seok Won Chang</name><name sortKey="Cheon, Chunhoo" sort="Cheon, Chunhoo" uniqKey="Cheon C" first="Chunhoo" last="Cheon">Chunhoo Cheon</name><name sortKey="Hong, Se Hyang" sort="Hong, Se Hyang" uniqKey="Hong S" first="Se Hyang" last="Hong">Se Hyang Hong</name><name sortKey="Ju, Sung Wan" sort="Ju, Sung Wan" uniqKey="Ju S" first="Sung Wan" last="Ju">Sung Wan Ju</name><name sortKey="Kim, Hyo In" sort="Kim, Hyo In" uniqKey="Kim H" first="Hyo In" last="Kim">Hyo In Kim</name><name sortKey="Kim, Min Jeong" sort="Kim, Min Jeong" uniqKey="Kim M" first="Min Jeong" last="Kim">Min Jeong 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></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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