Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression
Cervical cancer is a common gynecological malignancy afflicting women all over the world. Ginsenoside Rh2 (GRh2), especially 20(S)-GRh2, is a biologically active component in the natural plant ginseng, which can exhibit anticancer effects. Here, we aimed to investigate the effect of 20(S)-GRh2 on ce...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/22/7865 |
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| author | Ying Liu Xinran Wang Juhui Qiao Jiawen Wang Leilei Jiang Chenxi Wang Shiting Yu Peiguang Zhang Daqing Zhao Meiling Fan Meichen Liu |
| author_facet | Ying Liu Xinran Wang Juhui Qiao Jiawen Wang Leilei Jiang Chenxi Wang Shiting Yu Peiguang Zhang Daqing Zhao Meiling Fan Meichen Liu |
| author_sort | Ying Liu |
| collection | DOAJ |
| description | Cervical cancer is a common gynecological malignancy afflicting women all over the world. Ginsenoside Rh2 (GRh2), especially 20(S)-GRh2, is a biologically active component in the natural plant ginseng, which can exhibit anticancer effects. Here, we aimed to investigate the effect of 20(S)-GRh2 on cervical cancer and elucidate the underlying mechanism through RNA-seq. In this study, the CCK-8 assay showed that 20(S)-GRh2 inhibited HeLa cell viability in a time- and dose-dependent manner. Caspase 3 activity and Annexin V staining results showed that 20(S)-GRh2 induced apoptosis of HeLa cells. Gene function enrichment analysis revealed that the biological process gene ontology (GO) terms were associated with the apoptotic signaling pathway. Biological process GO terms’ similarity network indicated that apoptosis might be from endoplasmic reticulum stress (ERs). Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that 20(S)-GRh2 primarily modulates apoptosis pathway genes. Combined protein–protein interaction network, hub gene screening, and qPCR validation data showed that ERs-related genes (ATF4 and DDIT3) and the downstream apoptotic genes (JUN, FOS, BBC3, and PMAIP1) were potential novel targets of 20(S)-GRh2-inducing cervical cancer cell apoptosis. Differential transcript usage analysis indicated that DDIT3 is also a differential transcript and its usage of the isoform (ENST00000552740.5) was reduced by 20(S)-GRh2. Molecular docking suggested that 20(S)-GRh2 binds to the targets (ATF4, DDIT3, JUN, FOS, BBC3, and PMAIP1) with high affinity. In conclusion, our findings indicated that 20(S)-GRh2 might promote ERs-related apoptosis of cervical cancer cells by regulating the DDIT3-based targets’ signal pathway. The role of 20(S)-GRh2 at the transcriptome level provides novel targets and evidence for the treatment of cervical cancer. |
| first_indexed | 2024-03-09T18:06:54Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:06:54Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-630c501f0d844561a7556488b91918972023-11-24T09:22:27ZengMDPI AGMolecules1420-30492022-11-012722786510.3390/molecules27227865Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene ExpressionYing Liu0Xinran Wang1Juhui Qiao2Jiawen Wang3Leilei Jiang4Chenxi Wang5Shiting Yu6Peiguang Zhang7Daqing Zhao8Meiling Fan9Meichen Liu10Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaChangchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaDepartment of Obstetrics and Gynecology, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaCervical cancer is a common gynecological malignancy afflicting women all over the world. Ginsenoside Rh2 (GRh2), especially 20(S)-GRh2, is a biologically active component in the natural plant ginseng, which can exhibit anticancer effects. Here, we aimed to investigate the effect of 20(S)-GRh2 on cervical cancer and elucidate the underlying mechanism through RNA-seq. In this study, the CCK-8 assay showed that 20(S)-GRh2 inhibited HeLa cell viability in a time- and dose-dependent manner. Caspase 3 activity and Annexin V staining results showed that 20(S)-GRh2 induced apoptosis of HeLa cells. Gene function enrichment analysis revealed that the biological process gene ontology (GO) terms were associated with the apoptotic signaling pathway. Biological process GO terms’ similarity network indicated that apoptosis might be from endoplasmic reticulum stress (ERs). Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that 20(S)-GRh2 primarily modulates apoptosis pathway genes. Combined protein–protein interaction network, hub gene screening, and qPCR validation data showed that ERs-related genes (ATF4 and DDIT3) and the downstream apoptotic genes (JUN, FOS, BBC3, and PMAIP1) were potential novel targets of 20(S)-GRh2-inducing cervical cancer cell apoptosis. Differential transcript usage analysis indicated that DDIT3 is also a differential transcript and its usage of the isoform (ENST00000552740.5) was reduced by 20(S)-GRh2. Molecular docking suggested that 20(S)-GRh2 binds to the targets (ATF4, DDIT3, JUN, FOS, BBC3, and PMAIP1) with high affinity. In conclusion, our findings indicated that 20(S)-GRh2 might promote ERs-related apoptosis of cervical cancer cells by regulating the DDIT3-based targets’ signal pathway. The role of 20(S)-GRh2 at the transcriptome level provides novel targets and evidence for the treatment of cervical cancer.https://www.mdpi.com/1420-3049/27/22/7865ginsenoside Rh2apoptosisRNA-seqcervical cancermolecular dockingendoplasmic reticulum stress |
| spellingShingle | Ying Liu Xinran Wang Juhui Qiao Jiawen Wang Leilei Jiang Chenxi Wang Shiting Yu Peiguang Zhang Daqing Zhao Meiling Fan Meichen Liu Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression Molecules ginsenoside Rh2 apoptosis RNA-seq cervical cancer molecular docking endoplasmic reticulum stress |
| title | Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression |
| title_full | Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression |
| title_fullStr | Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression |
| title_full_unstemmed | Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression |
| title_short | Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression |
| title_sort | ginsenoside rh2 induces hela apoptosis through upregulating endoplasmic reticulum stress related and downstream apoptotic gene expression |
| topic | ginsenoside Rh2 apoptosis RNA-seq cervical cancer molecular docking endoplasmic reticulum stress |
| url | https://www.mdpi.com/1420-3049/27/22/7865 |
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