1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis
Raddeanin A (RA) has indicated suppressive effects on various human tumor cells, and insufficient vitamin D was associated with human papillomavirus (HPV) persistence and gynecological tumors. However, combined effects of RA and vitamin D on HPV-positive cells remain elusive. Herein, we aimed to inv...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-01-01
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| Series: | Bioengineered |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21655979.2021.2005223 |
| _version_ | 1798033994697146368 |
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| author | Zhiyu Li Biyun Xu Yuexin Sun Lanbo Zhou Yue Tao Wenjun Hou Jun Bao Jun Liu Weixin Fan |
| author_facet | Zhiyu Li Biyun Xu Yuexin Sun Lanbo Zhou Yue Tao Wenjun Hou Jun Bao Jun Liu Weixin Fan |
| author_sort | Zhiyu Li |
| collection | DOAJ |
| description | Raddeanin A (RA) has indicated suppressive effects on various human tumor cells, and insufficient vitamin D was associated with human papillomavirus (HPV) persistence and gynecological tumors. However, combined effects of RA and vitamin D on HPV-positive cells remain elusive. Herein, we aimed to investigate the combined effects of RA and 1ɑ,25(OH)2D3 (VD3) on cellular viability and modulation of HPV18E6/E7, programmed cell death 1 ligand (PD-L1) and vitamin D receptor (VDR) expression in HeLa cells in vitro. HeLa cells were treated with RA alone or VD3 combined with RA. Cell viability was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), and apoptosis was detected by flow cytometry. Real-time PCR (qRT-PCR) and Western blot were used to determine the gene/protein expression levels. The autophagosomes were observed by Transmission electron microscopy (TEM). The result showed that cell viability was inhibited by RA, and apoptosis in HeLa cells treated with RA was elevated accordingly. The expression of Bax, Cleaved-caspase-3, Cleaved-caspase-9 and Cleaved-PARP increased, and Bcl-2 decreased. The autophagy was induced by RA, as evidenced by elevated autophagosomes and the increased LC3-II/I ratio and Beclin-1. The expression of HPV18E6/E7, PD-L1 and VDR was reduced by RA. Moreover, RA combined with VD3 had a stronger effect on HeLa cells than RA alone. In conclusion, RA inhibits HeLa proliferation and induces apoptosis and autophagy via suppressing HPV18E6/E7, PD-L1 and VDR, and VD3 showed reinforced effects of RA on HeLa cells. Therefore, combined usage of VD3 with RA might be a potential novel immunotherapy strategy for HPV-related diseases. |
| first_indexed | 2024-04-11T20:38:07Z |
| format | Article |
| id | doaj.art-ac35a0a801154d129d748d16caf3b907 |
| institution | Directory Open Access Journal |
| issn | 2165-5979 2165-5987 |
| language | English |
| last_indexed | 2024-04-11T20:38:07Z |
| publishDate | 2022-01-01 |
| publisher | Taylor & Francis Group |
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| series | Bioengineered |
| spelling | doaj.art-ac35a0a801154d129d748d16caf3b9072022-12-22T04:04:19ZengTaylor & Francis GroupBioengineered2165-59792165-59872022-01-0113135736910.1080/21655979.2021.200522320052231α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axisZhiyu Li0Biyun Xu1Yuexin Sun2Lanbo Zhou3Yue Tao4Wenjun Hou5Jun Bao6Jun Liu7Weixin Fan8Drum Tower School of Clinical Medicine, Nanjing Medical UniversityDrum Tower School of Clinical Medicine, Nanjing Medical UniversityDrum Tower School of Clinical Medicine, Nanjing Medical UniversityThe First Affiliated Hospital of Nanjing Medical UniversityDrum Tower School of Clinical Medicine, Nanjing Medical UniversityDrum Tower School of Clinical Medicine, Nanjing Medical UniversityDrum Tower School of Clinical Medicine, Nanjing Medical UniversityDrum Tower School of Clinical Medicine, Nanjing Medical UniversityThe First Affiliated Hospital of Nanjing Medical UniversityRaddeanin A (RA) has indicated suppressive effects on various human tumor cells, and insufficient vitamin D was associated with human papillomavirus (HPV) persistence and gynecological tumors. However, combined effects of RA and vitamin D on HPV-positive cells remain elusive. Herein, we aimed to investigate the combined effects of RA and 1ɑ,25(OH)2D3 (VD3) on cellular viability and modulation of HPV18E6/E7, programmed cell death 1 ligand (PD-L1) and vitamin D receptor (VDR) expression in HeLa cells in vitro. HeLa cells were treated with RA alone or VD3 combined with RA. Cell viability was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), and apoptosis was detected by flow cytometry. Real-time PCR (qRT-PCR) and Western blot were used to determine the gene/protein expression levels. The autophagosomes were observed by Transmission electron microscopy (TEM). The result showed that cell viability was inhibited by RA, and apoptosis in HeLa cells treated with RA was elevated accordingly. The expression of Bax, Cleaved-caspase-3, Cleaved-caspase-9 and Cleaved-PARP increased, and Bcl-2 decreased. The autophagy was induced by RA, as evidenced by elevated autophagosomes and the increased LC3-II/I ratio and Beclin-1. The expression of HPV18E6/E7, PD-L1 and VDR was reduced by RA. Moreover, RA combined with VD3 had a stronger effect on HeLa cells than RA alone. In conclusion, RA inhibits HeLa proliferation and induces apoptosis and autophagy via suppressing HPV18E6/E7, PD-L1 and VDR, and VD3 showed reinforced effects of RA on HeLa cells. Therefore, combined usage of VD3 with RA might be a potential novel immunotherapy strategy for HPV-related diseases.http://dx.doi.org/10.1080/21655979.2021.2005223vitamin draddeanin a (ra)hela cellsapoptosisautophagypd-l1 |
| spellingShingle | Zhiyu Li Biyun Xu Yuexin Sun Lanbo Zhou Yue Tao Wenjun Hou Jun Bao Jun Liu Weixin Fan 1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis Bioengineered vitamin d raddeanin a (ra) hela cells apoptosis autophagy pd-l1 |
| title | 1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis |
| title_full | 1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis |
| title_fullStr | 1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis |
| title_full_unstemmed | 1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis |
| title_short | 1α,25(OH)2D3(VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis |
| title_sort | 1α 25 oh 2d3 vd3 promotes raddeanin a induced anti proliferative effects on hela cell apoptosis and autophagy through negative regulation of hpv18e6 e7 pd l1 vdr axis |
| topic | vitamin d raddeanin a (ra) hela cells apoptosis autophagy pd-l1 |
| url | http://dx.doi.org/10.1080/21655979.2021.2005223 |
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