Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C-induced apoptosis in urinary bladder urothelial carcinoma cells.
Identifieur interne : 000C35 ( Main/Exploration ); précédent : 000C34; suivant : 000C36Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C-induced apoptosis in urinary bladder urothelial carcinoma cells.
Auteurs : Sheng-Yuan Huang [Taïwan] ; Chih-Cheng Chien [Taïwan] ; Ruey-Shyang Hseu [Taïwan] ; Victoria Ying Jen Huang [Canada] ; Shang Ying Chiang [Canada] ; Chi-Jung Huang [Taïwan] ; Shao-Kuan Chen [Taïwan] ; Ru-Yin Tsai [Taïwan] ; Hsi-Ting Lin [Taïwan] ; Yu-Che Cheng [Taïwan]Source :
- Journal of cellular biochemistry [ 1097-4644 ] ; 2018.
Descripteurs français
- KwdFr :
- Apoptose (), Facteurs immunologiques (pharmacologie), Ganoderma (), Humains, Lignée cellulaire tumorale, Mitomycine (pharmacologie), Protéines fongiques (pharmacologie), Protéines tumorales (biosynthèse), Régulation de l'expression des gènes tumoraux (), Tumeurs de la vessie urinaire (anatomopathologie), Tumeurs de la vessie urinaire (métabolisme), Tumeurs de la vessie urinaire (traitement médicamenteux).
- MESH :
- anatomopathologie : Tumeurs de la vessie urinaire.
- biosynthèse : Protéines tumorales.
- métabolisme : Tumeurs de la vessie urinaire.
- pharmacologie : Facteurs immunologiques, Mitomycine, Protéines fongiques.
- traitement médicamenteux : Tumeurs de la vessie urinaire.
- Apoptose, Ganoderma, Humains, Lignée cellulaire tumorale, Régulation de l'expression des gènes tumoraux.
English descriptors
- KwdEn :
- Apoptosis (drug effects), Cell Line, Tumor, Fungal Proteins (pharmacology), Ganoderma (chemistry), Gene Expression Regulation, Neoplastic (drug effects), Humans, Immunologic Factors (pharmacology), Mitomycin (pharmacology), Neoplasm Proteins (biosynthesis), Urinary Bladder Neoplasms (drug therapy), Urinary Bladder Neoplasms (metabolism), Urinary Bladder Neoplasms (pathology).
- MESH :
- chemical , biosynthesis : Neoplasm Proteins.
- chemical , pharmacology : Fungal Proteins, Immunologic Factors, Mitomycin.
- chemistry : Ganoderma.
- drug effects : Apoptosis, Gene Expression Regulation, Neoplastic.
- drug therapy : Urinary Bladder Neoplasms.
- metabolism : Urinary Bladder Neoplasms.
- pathology : Urinary Bladder Neoplasms.
- Cell Line, Tumor, Humans.
Abstract
Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.
DOI: 10.1002/jcb.26616
PubMed: 29240252
Affiliations:
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wicri:level="1"><nlm:affiliation>Proteomics Laboratory, Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Proteomics Laboratory, Department of Medical Research, Cathay General Hospital, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Chien, Chih Cheng" sort="Chien, Chih Cheng" uniqKey="Chien C" first="Chih-Cheng" last="Chien">Chih-Cheng Chien</name><affiliation wicri:level="1"><nlm:affiliation>School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Medicine, Fu Jen Catholic University, New Taipei City</wicri:regionArea><wicri:noRegion>New Taipei City</wicri:noRegion></affiliation></author><author><name sortKey="Hseu, Ruey Shyang" sort="Hseu, Ruey Shyang" uniqKey="Hseu R" first="Ruey-Shyang" last="Hseu">Ruey-Shyang Hseu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biochemical Science and Technology, National Taiwan University, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Victoria Ying Jen" sort="Huang, Victoria Ying Jen" uniqKey="Huang V" first="Victoria Ying Jen" last="Huang">Victoria Ying Jen Huang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, Toronto</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Chiang, Shang Ying" sort="Chiang, Shang Ying" uniqKey="Chiang S" first="Shang Ying" last="Chiang">Shang Ying Chiang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, Toronto</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Huang, Chi Jung" sort="Huang, Chi Jung" uniqKey="Huang C" first="Chi-Jung" last="Huang">Chi-Jung Huang</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Gene Laboratory, Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Clinical Gene Laboratory, Department of Medical Research, Cathay General Hospital, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Shao Kuan" sort="Chen, Shao Kuan" uniqKey="Chen S" first="Shao-Kuan" last="Chen">Shao-Kuan Chen</name><affiliation wicri:level="1"><nlm:affiliation>School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>School of Medicine, Fu Jen Catholic University, New Taipei City</wicri:regionArea><wicri:noRegion>New Taipei City</wicri:noRegion></affiliation></author><author><name sortKey="Tsai, Ru Yin" sort="Tsai, Ru Yin" uniqKey="Tsai R" first="Ru-Yin" last="Tsai">Ru-Yin Tsai</name><affiliation wicri:level="1"><nlm:affiliation>College of Nursing and Health Science, Da-Yeh University, Changhua, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>College of Nursing and Health Science, Da-Yeh University, Changhua</wicri:regionArea><wicri:noRegion>Changhua</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Hsi Ting" sort="Lin, Hsi Ting" uniqKey="Lin H" first="Hsi-Ting" last="Lin">Hsi-Ting Lin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Surgery, Cathay General Hospital, Taipei, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Surgery, Cathay General Hospital, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Cheng, Yu Che" sort="Cheng, Yu Che" uniqKey="Cheng Y" first="Yu-Che" last="Cheng">Yu-Che Cheng</name><affiliation wicri:level="1"><nlm:affiliation>Proteomics Laboratory, Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Proteomics Laboratory, Department of Medical Research, Cathay General Hospital, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of cellular biochemistry</title><idno type="eISSN">1097-4644</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis (drug effects)</term><term>Cell Line, Tumor</term><term>Fungal Proteins (pharmacology)</term><term>Ganoderma (chemistry)</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>Humans</term><term>Immunologic Factors (pharmacology)</term><term>Mitomycin (pharmacology)</term><term>Neoplasm Proteins (biosynthesis)</term><term>Urinary Bladder Neoplasms (drug therapy)</term><term>Urinary Bladder Neoplasms (metabolism)</term><term>Urinary Bladder Neoplasms (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Apoptose ()</term><term>Facteurs immunologiques (pharmacologie)</term><term>Ganoderma ()</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mitomycine (pharmacologie)</term><term>Protéines fongiques (pharmacologie)</term><term>Protéines tumorales (biosynthèse)</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Tumeurs de la vessie urinaire (anatomopathologie)</term><term>Tumeurs de la vessie urinaire (métabolisme)</term><term>Tumeurs de la vessie urinaire (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Neoplasm Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Fungal Proteins</term><term>Immunologic Factors</term><term>Mitomycin</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs de la vessie urinaire</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Protéines tumorales</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Ganoderma</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Gene Expression Regulation, Neoplastic</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Urinary Bladder Neoplasms</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Urinary Bladder Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Tumeurs de la vessie urinaire</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Urinary Bladder Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Facteurs immunologiques</term><term>Mitomycine</term><term>Protéines fongiques</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs de la vessie urinaire</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Apoptose</term><term>Ganoderma</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Régulation de l'expression des gènes tumoraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC<sub>50</sub> ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Taïwan</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Taïwan"><noRegion><name sortKey="Huang, Sheng Yuan" sort="Huang, Sheng Yuan" uniqKey="Huang S" first="Sheng-Yuan" last="Huang">Sheng-Yuan Huang</name></noRegion><name sortKey="Chen, Shao Kuan" sort="Chen, Shao Kuan" uniqKey="Chen S" first="Shao-Kuan" last="Chen">Shao-Kuan Chen</name><name sortKey="Cheng, Yu Che" sort="Cheng, Yu Che" uniqKey="Cheng Y" first="Yu-Che" last="Cheng">Yu-Che Cheng</name><name sortKey="Chien, Chih Cheng" sort="Chien, Chih Cheng" uniqKey="Chien C" first="Chih-Cheng" last="Chien">Chih-Cheng Chien</name><name sortKey="Hseu, Ruey Shyang" sort="Hseu, Ruey Shyang" uniqKey="Hseu R" first="Ruey-Shyang" last="Hseu">Ruey-Shyang Hseu</name><name sortKey="Huang, Chi Jung" sort="Huang, Chi Jung" uniqKey="Huang C" first="Chi-Jung" last="Huang">Chi-Jung Huang</name><name sortKey="Lin, Hsi Ting" sort="Lin, Hsi Ting" uniqKey="Lin H" first="Hsi-Ting" last="Lin">Hsi-Ting Lin</name><name sortKey="Tsai, Ru Yin" sort="Tsai, Ru Yin" uniqKey="Tsai R" first="Ru-Yin" last="Tsai">Ru-Yin Tsai</name></country><country name="Canada"><region name="Ontario"><name sortKey="Huang, Victoria Ying Jen" sort="Huang, Victoria Ying Jen" uniqKey="Huang V" first="Victoria Ying Jen" last="Huang">Victoria Ying Jen Huang</name></region><name sortKey="Chiang, Shang Ying" sort="Chiang, Shang Ying" uniqKey="Chiang S" first="Shang Ying" last="Chiang">Shang Ying Chiang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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