Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer...
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MDPI AG
2017-02-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/2/276 |
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| author | Seung Ho Baek Jong Hyun Lee Chulwon Kim Jeong-Hyeon Ko Seung-Hee Ryu Seok-Geun Lee Woong Mo Yang Jae-Young Um Arunachalam Chinnathambi Sulaiman Ali Alharbi Gautam Sethi Kwang Seok Ahn |
| author_facet | Seung Ho Baek Jong Hyun Lee Chulwon Kim Jeong-Hyeon Ko Seung-Hee Ryu Seok-Geun Lee Woong Mo Yang Jae-Young Um Arunachalam Chinnathambi Sulaiman Ali Alharbi Gautam Sethi Kwang Seok Ahn |
| author_sort | Seung Ho Baek |
| collection | DOAJ |
| description | Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP) inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells. |
| first_indexed | 2024-04-13T19:10:04Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T19:10:04Z |
| publishDate | 2017-02-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3bd63f6e7d7d4729bba97e73d50003792022-12-22T02:33:52ZengMDPI AGMolecules1420-30492017-02-0122227610.3390/molecules22020276molecules22020276Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine PhosphataseSeung Ho Baek0Jong Hyun Lee1Chulwon Kim2Jeong-Hyeon Ko3Seung-Hee Ryu4Seok-Geun Lee5Woong Mo Yang6Jae-Young Um7Arunachalam Chinnathambi8Sulaiman Ali Alharbi9Gautam Sethi10Kwang Seok Ahn11College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaDepartment of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, KoreaGinkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP) inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells.http://www.mdpi.com/1420-3049/22/2/276ginkgolic acid C 17:1STAT3PTENSHP-1apoptosis |
| spellingShingle | Seung Ho Baek Jong Hyun Lee Chulwon Kim Jeong-Hyeon Ko Seung-Hee Ryu Seok-Geun Lee Woong Mo Yang Jae-Young Um Arunachalam Chinnathambi Sulaiman Ali Alharbi Gautam Sethi Kwang Seok Ahn Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase Molecules ginkgolic acid C 17:1 STAT3 PTEN SHP-1 apoptosis |
| title | Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase |
| title_full | Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase |
| title_fullStr | Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase |
| title_full_unstemmed | Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase |
| title_short | Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase |
| title_sort | ginkgolic acid c 17 1 derived from ginkgo biloba leaves suppresses constitutive and inducible stat3 activation through induction of pten and shp 1 tyrosine phosphatase |
| topic | ginkgolic acid C 17:1 STAT3 PTEN SHP-1 apoptosis |
| url | http://www.mdpi.com/1420-3049/22/2/276 |
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