Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging
Derived from Panax ginseng, the natural product 20(S)-Protopanaxadiol (PPD) has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes G2/...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/22/3/486 |
| _version_ | 1818206221300137984 |
|---|---|
| author | Bo Teng Junguang Jiang Lijing Zhao Jing Gao Junyu Chen Zhe Liu Hongda Wang Binfeng Lu |
| author_facet | Bo Teng Junguang Jiang Lijing Zhao Jing Gao Junyu Chen Zhe Liu Hongda Wang Binfeng Lu |
| author_sort | Bo Teng |
| collection | DOAJ |
| description | Derived from Panax ginseng, the natural product 20(S)-Protopanaxadiol (PPD) has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes G2/M cell cycle arrest in human laryngeal carcinoma cells (Hep-2 cells). PPD also decreases the levels of proteins related to cell proliferation. Moreover, PPD-induced apoptosis is characterized by a dose-dependent down-regulation of Bcl-2 expression and up-regulation of Bax, and is accompanied by the activation of Caspase-3 as well. Further molecular mechanism is revealed by direct stochastic optical reconstruction microscopy (dSTORM)—a novel high-precision localization microscopy which enables effective resolution down to the order of 10 nm. It shows the expression and spatial arrangement of mTOR and its downstream effectors, demonstrating that this ginsenoside exerts its excellent anticancer effects via down-regulation of mTOR signaling pathway in Hep-2 cells. Taken together, our findings elucidate that the antitumor effect of PPD is associated with its regulation of mTOR expression and distribution, which encourages further studies of PPD as a promising therapeutic agent against laryngeal carcinoma. |
| first_indexed | 2024-12-12T04:09:35Z |
| format | Article |
| id | doaj.art-84f4df9c46b2442b86a21414ec2cda02 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T04:09:35Z |
| publishDate | 2017-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-84f4df9c46b2442b86a21414ec2cda022022-12-22T00:38:41ZengMDPI AGMolecules1420-30492017-03-0122348610.3390/molecules22030486molecules22030486Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution ImagingBo Teng0Junguang Jiang1Lijing Zhao2Jing Gao3Junyu Chen4Zhe Liu5Hongda Wang6Binfeng Lu7Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun 13041, Jilin, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 13021, Jilin, ChinaSchool of Nursing, Jilin University, Changchun 13021, Jilin, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 13021, Jilin, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun 13041, Jilin, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun 13041, Jilin, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 13021, Jilin, ChinaDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USADerived from Panax ginseng, the natural product 20(S)-Protopanaxadiol (PPD) has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes G2/M cell cycle arrest in human laryngeal carcinoma cells (Hep-2 cells). PPD also decreases the levels of proteins related to cell proliferation. Moreover, PPD-induced apoptosis is characterized by a dose-dependent down-regulation of Bcl-2 expression and up-regulation of Bax, and is accompanied by the activation of Caspase-3 as well. Further molecular mechanism is revealed by direct stochastic optical reconstruction microscopy (dSTORM)—a novel high-precision localization microscopy which enables effective resolution down to the order of 10 nm. It shows the expression and spatial arrangement of mTOR and its downstream effectors, demonstrating that this ginsenoside exerts its excellent anticancer effects via down-regulation of mTOR signaling pathway in Hep-2 cells. Taken together, our findings elucidate that the antitumor effect of PPD is associated with its regulation of mTOR expression and distribution, which encourages further studies of PPD as a promising therapeutic agent against laryngeal carcinoma.http://www.mdpi.com/1420-3049/22/3/486PPDlaryngeal cancermTORantitumordSTORM |
| spellingShingle | Bo Teng Junguang Jiang Lijing Zhao Jing Gao Junyu Chen Zhe Liu Hongda Wang Binfeng Lu Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging Molecules PPD laryngeal cancer mTOR antitumor dSTORM |
| title | Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging |
| title_full | Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging |
| title_fullStr | Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging |
| title_full_unstemmed | Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging |
| title_short | Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging |
| title_sort | ginsenoside ppd s antitumor effect via down regulation of mtor revealed by super resolution imaging |
| topic | PPD laryngeal cancer mTOR antitumor dSTORM |
| url | http://www.mdpi.com/1420-3049/22/3/486 |
| work_keys_str_mv | AT boteng ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT junguangjiang ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT lijingzhao ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT jinggao ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT junyuchen ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT zheliu ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT hongdawang ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging AT binfenglu ginsenosideppdsantitumoreffectviadownregulationofmtorrevealedbysuperresolutionimaging |