Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells
Abstract Background Vasculogenic mimicry (VM) is characterized by the formation of tubular structure inside the tumor stroma. It has been shown that a small fraction of cancer cells, namely cancer stem cells (CSCs), could stimulate the development of vascular units in the tumor niche, leading to enh...
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-021-03246-w |
| _version_ | 1818610493918543872 |
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| author | Sanya Haiaty Mohammad-Reza Rashidi Maryam Akbarzadeh Ahad Bazmany Mostafa Mostafazadeh Saba Nikanfar Zohre Zibaei Reza Rahbarghazi Mohammad Nouri |
| author_facet | Sanya Haiaty Mohammad-Reza Rashidi Maryam Akbarzadeh Ahad Bazmany Mostafa Mostafazadeh Saba Nikanfar Zohre Zibaei Reza Rahbarghazi Mohammad Nouri |
| author_sort | Sanya Haiaty |
| collection | DOAJ |
| description | Abstract Background Vasculogenic mimicry (VM) is characterized by the formation of tubular structure inside the tumor stroma. It has been shown that a small fraction of cancer cells, namely cancer stem cells (CSCs), could stimulate the development of vascular units in the tumor niche, leading to enhanced metastasis to the remote sites. This study aimed to study the inhibitory effect of phytocompound, Thymoquinone (TQ), on human breast MDA-MB-231 cell line via monitoring Wnt/PI3K signaling pathway. Methods MDA-MB-231 CSCs were incubated with different concentrations of TQ for 48 h. The viability of CSCs was determined using the MTT assay. The combination of TQ and PI3K and Wnt3a inhibitors was examined in CSCs. By using the Matrigel assay, we measured the tubulogenesis capacity. The percent of CD24− CSCs and Rhodamine 123 efflux capacity was studied using flow cytometry analysis. Protein levels of Akt, p-Akt, Wnt3a, vascular endothelial-cadherin (VE-cadherin), and matrix metalloproteinases-2 and -9 (MMP-2 and -9) were detected by western blotting. Results TQ decreased the viability of CSCs in a dose-dependent manner. The combination of TQ with PI3K and Wnt3a inhibitors reduced significantly the survival rate compared to the control group (p < 0.05). TQ could blunt the stimulatory effect of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) on CSCs (p < 0.05). The vasculogenic capacity of CSCs was reduced after being-exposed to TQ (p < 0.05). Western blotting revealed the decrease of CSCs metastasis by suppressing MMP-2 and -9. The protein level of VE-cadherin was also diminished in TQ-treated CSCs as compared to the control cell (p < 0.05), indicating inhibition of mesenchymal-endothelial transition (MendT). TQ could suppress Wnt3a and PI3K, which coincided with the reduction of the p-Akt/Akt ratio. TQ had the potential to decrease the number of CD24− CSCs and Rhodamine 123 efflux capacity after 48 h. Conclusion TQ could alter the vasculogenic capacity and mesenchymal-epithelial transition of human breast CSCs in vitro. Thus TQ together with anti-angiogenic therapies may be a novel therapeutic agent in the suppression of VM in breast cancer. |
| first_indexed | 2024-12-16T15:15:19Z |
| format | Article |
| id | doaj.art-b4a1d612304741268619a672be43b69d |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-12-16T15:15:19Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-b4a1d612304741268619a672be43b69d2022-12-21T22:26:50ZengBMCBMC Complementary Medicine and Therapies2662-76712021-03-0121111210.1186/s12906-021-03246-wThymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cellsSanya Haiaty0Mohammad-Reza Rashidi1Maryam Akbarzadeh2Ahad Bazmany3Mostafa Mostafazadeh4Saba Nikanfar5Zohre Zibaei6Reza Rahbarghazi7Mohammad Nouri8Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical SciencesStem Cell and Regenerative Medicine Institute, Tabriz University of Medical SciencesDepartment of Biochemistry and Clinical Laboratories, Tabriz University of Medical SciencesDepartment of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University Of MashhadDepartment of Biochemistry and Clinical Laboratories, Tabriz University of Medical SciencesDepartment of Biochemistry and Clinical Laboratories, Tabriz University of Medical SciencesStudent Research Committee, Tabriz University of Medical SciencesStem Cell and Regenerative Medicine Institute, Tabriz University of Medical SciencesDepartment of Biochemistry and Clinical Laboratories, Tabriz University of Medical SciencesAbstract Background Vasculogenic mimicry (VM) is characterized by the formation of tubular structure inside the tumor stroma. It has been shown that a small fraction of cancer cells, namely cancer stem cells (CSCs), could stimulate the development of vascular units in the tumor niche, leading to enhanced metastasis to the remote sites. This study aimed to study the inhibitory effect of phytocompound, Thymoquinone (TQ), on human breast MDA-MB-231 cell line via monitoring Wnt/PI3K signaling pathway. Methods MDA-MB-231 CSCs were incubated with different concentrations of TQ for 48 h. The viability of CSCs was determined using the MTT assay. The combination of TQ and PI3K and Wnt3a inhibitors was examined in CSCs. By using the Matrigel assay, we measured the tubulogenesis capacity. The percent of CD24− CSCs and Rhodamine 123 efflux capacity was studied using flow cytometry analysis. Protein levels of Akt, p-Akt, Wnt3a, vascular endothelial-cadherin (VE-cadherin), and matrix metalloproteinases-2 and -9 (MMP-2 and -9) were detected by western blotting. Results TQ decreased the viability of CSCs in a dose-dependent manner. The combination of TQ with PI3K and Wnt3a inhibitors reduced significantly the survival rate compared to the control group (p < 0.05). TQ could blunt the stimulatory effect of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) on CSCs (p < 0.05). The vasculogenic capacity of CSCs was reduced after being-exposed to TQ (p < 0.05). Western blotting revealed the decrease of CSCs metastasis by suppressing MMP-2 and -9. The protein level of VE-cadherin was also diminished in TQ-treated CSCs as compared to the control cell (p < 0.05), indicating inhibition of mesenchymal-endothelial transition (MendT). TQ could suppress Wnt3a and PI3K, which coincided with the reduction of the p-Akt/Akt ratio. TQ had the potential to decrease the number of CD24− CSCs and Rhodamine 123 efflux capacity after 48 h. Conclusion TQ could alter the vasculogenic capacity and mesenchymal-epithelial transition of human breast CSCs in vitro. Thus TQ together with anti-angiogenic therapies may be a novel therapeutic agent in the suppression of VM in breast cancer.https://doi.org/10.1186/s12906-021-03246-wThymoquinoneVasculogenic mimicryBreast Cancer stem cellsWnt3a/PI3K signaling pathways |
| spellingShingle | Sanya Haiaty Mohammad-Reza Rashidi Maryam Akbarzadeh Ahad Bazmany Mostafa Mostafazadeh Saba Nikanfar Zohre Zibaei Reza Rahbarghazi Mohammad Nouri Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells BMC Complementary Medicine and Therapies Thymoquinone Vasculogenic mimicry Breast Cancer stem cells Wnt3a/PI3K signaling pathways |
| title | Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells |
| title_full | Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells |
| title_fullStr | Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells |
| title_full_unstemmed | Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells |
| title_short | Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells |
| title_sort | thymoquinone inhibited vasculogenic capacity and promoted mesenchymal epithelial transition of human breast cancer stem cells |
| topic | Thymoquinone Vasculogenic mimicry Breast Cancer stem cells Wnt3a/PI3K signaling pathways |
| url | https://doi.org/10.1186/s12906-021-03246-w |
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