Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells
Purpose: The hypoxia in solid tumors is associated with the resistance to chemo/radiotherapy.Hypoxia-inducible factor-1 (HIF-1) plays a key role in cell remodeling to hypoxia. Therefore, theinhibition of HIF-1 accumulation is considered a hopeful strategy for the treatment of cancer.Here, we aimed t...
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2022-05-01
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| Series: | Advanced Pharmaceutical Bulletin |
| Subjects: | |
| Online Access: | https://apb.tbzmed.ac.ir/PDF/apb-12-593.pdf |
| _version_ | 1811219285789376512 |
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| author | Somayeh Vandghanooni Zahra Farajzadeh Vahid Ailar Nakhlband Mir Babak Bahadori Morteza Eskandani |
| author_facet | Somayeh Vandghanooni Zahra Farajzadeh Vahid Ailar Nakhlband Mir Babak Bahadori Morteza Eskandani |
| author_sort | Somayeh Vandghanooni |
| collection | DOAJ |
| description | Purpose: The hypoxia in solid tumors is associated with the resistance to chemo/radiotherapy.Hypoxia-inducible factor-1 (HIF-1) plays a key role in cell remodeling to hypoxia. Therefore, theinhibition of HIF-1 accumulation is considered a hopeful strategy for the treatment of cancer.Here, we aimed to evaluate the geno- and cytotoxicity properties of sclareol, a natural bicyclicditerpene alcohol, on A549 cells in CoCl2-induced hypoxia.Methods: The cytotoxicity and apoptosis-inducing properties of sclareol on the A549 cell wereevaluated using MTT assay and Annexin V/PI staining, respectively in hypoxia. DAPI staining,DNA ladder, and comet assay were used to evaluate the genotoxicity. Further, the qPCRtechnique was employed to assess the expression of HIF-1α, HIF-1β, and downstream targetgenes (GluT1, and Eno1). Finally, the level of HIF-1α protein was evaluated through Westernblotting in sclareol-treated cells in hypoxia.Results: The inhibitory concentration (IC50) of sclareol against A549 cells was 8 μg/mL at 48hours in hypoxia. The genotoxicity of sclareol was confirmed in the cells treated with sclareolin hypoxia. Sclareol induced ~46% apoptosis and also necrosis in the hypoxic condition. TheqPCR analyses showed an enhanced suppression of HIF-1α, HIF-1β, GluT1, and Eno1 due tothe sclareol treatment in the hypoxia. Moreover, protein quantification analysis showed dosedependentlydegradation of HIF-1α in hypoxia upon treatment with sclareol.Conclusion: The results obtained here indicate that sclareol possesses dose-dependentcytotoxicity effects against A549 cells in hypoxia through inhibition of HIF-1α proteinaccumulation, increasing cell sensitivity to intracellular oxygen levels, and disruption of celladaptation to hypoxia. |
| first_indexed | 2024-04-12T07:23:35Z |
| format | Article |
| id | doaj.art-4f67eb6591574c32a5764dbd244b5d25 |
| institution | Directory Open Access Journal |
| issn | 2228-5881 2251-7308 |
| language | English |
| last_indexed | 2024-04-12T07:23:35Z |
| publishDate | 2022-05-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Advanced Pharmaceutical Bulletin |
| spelling | doaj.art-4f67eb6591574c32a5764dbd244b5d252022-12-22T03:42:14ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082022-05-0112359360210.34172/apb.2022.062apb-32381Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer CellsSomayeh Vandghanooni0Zahra Farajzadeh Vahid1Ailar Nakhlband2Mir Babak Bahadori3Morteza Eskandani4Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Faculty of Natural Sciences, Department of Biology, University of Tabriz, Tabriz, Iran.Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran.Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.Purpose: The hypoxia in solid tumors is associated with the resistance to chemo/radiotherapy.Hypoxia-inducible factor-1 (HIF-1) plays a key role in cell remodeling to hypoxia. Therefore, theinhibition of HIF-1 accumulation is considered a hopeful strategy for the treatment of cancer.Here, we aimed to evaluate the geno- and cytotoxicity properties of sclareol, a natural bicyclicditerpene alcohol, on A549 cells in CoCl2-induced hypoxia.Methods: The cytotoxicity and apoptosis-inducing properties of sclareol on the A549 cell wereevaluated using MTT assay and Annexin V/PI staining, respectively in hypoxia. DAPI staining,DNA ladder, and comet assay were used to evaluate the genotoxicity. Further, the qPCRtechnique was employed to assess the expression of HIF-1α, HIF-1β, and downstream targetgenes (GluT1, and Eno1). Finally, the level of HIF-1α protein was evaluated through Westernblotting in sclareol-treated cells in hypoxia.Results: The inhibitory concentration (IC50) of sclareol against A549 cells was 8 μg/mL at 48hours in hypoxia. The genotoxicity of sclareol was confirmed in the cells treated with sclareolin hypoxia. Sclareol induced ~46% apoptosis and also necrosis in the hypoxic condition. TheqPCR analyses showed an enhanced suppression of HIF-1α, HIF-1β, GluT1, and Eno1 due tothe sclareol treatment in the hypoxia. Moreover, protein quantification analysis showed dosedependentlydegradation of HIF-1α in hypoxia upon treatment with sclareol.Conclusion: The results obtained here indicate that sclareol possesses dose-dependentcytotoxicity effects against A549 cells in hypoxia through inhibition of HIF-1α proteinaccumulation, increasing cell sensitivity to intracellular oxygen levels, and disruption of celladaptation to hypoxia.https://apb.tbzmed.ac.ir/PDF/apb-12-593.pdfsclareolnatural compounda549lung cancerhypoxiahif-1α |
| spellingShingle | Somayeh Vandghanooni Zahra Farajzadeh Vahid Ailar Nakhlband Mir Babak Bahadori Morteza Eskandani Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells Advanced Pharmaceutical Bulletin sclareol natural compound a549 lung cancer hypoxia hif-1α |
| title | Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells |
| title_full | Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells |
| title_fullStr | Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells |
| title_full_unstemmed | Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells |
| title_short | Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells |
| title_sort | sclareol inhibits hypoxia inducible factor 1α accumulation and induces apoptosis in hypoxic cancer cells |
| topic | sclareol natural compound a549 lung cancer hypoxia hif-1α |
| url | https://apb.tbzmed.ac.ir/PDF/apb-12-593.pdf |
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