Emblica officinalis extract downregulates pro-angiogenic molecules via upregulation of cellular and exosomal miR-375 in human ovarian cancer cells
| Autor: | Ajay Bansal, Siddarth Sharma, Archana De, Peter J. Van Veldhuizen, Jianping Zhou, Mukut Sharma, Ramratan Sharma, Benjamin Powers, Alok De |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
microRNA-375 Down-Regulation Phyllanthus emblica exosomes Receptor IGF Type 1 03 medical and health sciences Downregulation and upregulation In vivo Mir-375 Antigens CD IGF1R Cell Line Tumor medicine Humans Insulin-like growth factor 1 receptor Ovarian Neoplasms Tumor microenvironment business.industry Plant Extracts Receptors Somatomedin medicine.disease Cadherins Xenograft Model Antitumor Assays In vitro Tumor Burden Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology ovarian cancer Oncology Cancer cell Immunology Cancer research Female Snail Family Transcription Factors Emblica officinalis Ovarian cancer business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Ovarian cancer (OC) is highly resistant to current treatment strategies based on a combination of surgery, chemotherapy and radiation therapy. We have recently demonstrated the anti-neoplastic effect of Amla extract (Emblica officinalis, AE) on OC cells in vitro and in vivo. We hypothesized that AE attenuates growth of OC through microRNA (miR)-regulated mechanism(s). The inhibitory effect of AE on proliferation, migration and invasiveness (P≤0.001) of SKOV3 cells and >90% attenuation of tumor growth in a xenograft mouse model suggested multiple targets. RT-qPCR analysis of microRNAs associated with OC showed a >2,000-fold increase in the expression of miR-375 in AE-treated SKOV3 cells that was blocked by an exogenous miR-375 inhibitor (P≤0.001). AE also decreased the gene and protein expression of IGF1R, a target of miR-375 (P≤0.001), and SNAIL1 (P≤0.002), an EMT-associated transcription factor that represses E-cadherin expression (P≤0.003). AE increased E-cadherin expression (P≤0.001). Treatment of SKOV3 cells with AE resulted in increased miR-375 in exosomes in the medium (P≤0.01). Finally, AE significantly decreased the expression of IGF1R and SNAIL1 proteins during attenuation of SKOV3-derived xenograft tumor. Together, these results show that AE modulates cancer cells and the tumor microenvironment via activation of miR-375 and by targeting IGF1R and SNAIL1 in OC cells. |
| Databáze: | OpenAIRE |
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