Academic Journal
Botox-A induced apoptosis and suppressed cell proliferation in fibroblasts pre-treated with breast cancer exosomes
| Title: | Botox-A induced apoptosis and suppressed cell proliferation in fibroblasts pre-treated with breast cancer exosomes |
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| Authors: | Hossein Sayaf, Niloufar Salimian, Mahnaz Mohammadi, Parisa Ahmadi, Amir Gholamzad, Sadegh Babashah, Maliheh Entezari, Najma Farahani, Maryam Montazeri, Mehrdad Hashemi |
| Source: | Molecular and Cellular Probes, Vol 79, Iss , Pp 102007- (2025) |
| Publisher Information: | Elsevier, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Biology (General) LCC:Medicine |
| Subject Terms: | Breast cancer, Botulinum, lncRNA, Apoptosis, Epithelial-mesenchymal transition, Biology (General), QH301-705.5, Medicine |
| More Details: | Background: breast cancer-associated fibroblast (CAF) is linked to metastasis and is poor for breast cancer prognosis. Since Clostridium Toxin A (Botox-A) had represented a cytotoxic effect on fibroblasts, this study aims to assess Botox-A cytotoxicity in both normal fibroblasts and exosome-induced CAFs. Material and method: the serum exosomes of 40 BC patients and 30 healthy individuals were isolated and lncRNA H19 (lnch19) levels were assessed by qRT-PCR method. After that, Breast Cancer (BC) exosomes co-cultured with Human foreskin fibroblasts (HFF) and qRT-PCR were applied to evaluate α-SMA, Vimentin, BCL-2, and BAX expression. Both Normal and malignant HFFs co-cultured with Botox-A, and Botox-A loaded exosome for 24 and 48 h and their apoptosis, Cell proliferation, and viability were monitored by MTT assay, Annexin V-FITC and PI staining and qRT-PCR for BCL-2, BAX, and cyclin D1 mRNAs. Results: Serum exosomes of BC patients had significantly higher levels of lncRNA H19 than healthy individuals. MTT assay results showed Botox-A decreased vital Human foreskin fibroblasts in a dose-dependent manner. BC exosomes significantly increased α-SMA, Vimentin, and BCL-2 mRNA levels in Human foreskin fibroblasts, on the other hand, BAX decreased meaningfully. Co-culture of exosome-treated HFF cells with both Botox-A and Botox-A loaded exosomes significantly boosted BCL-2 mRNA levels, completely contrary to BAX and cyclid d1 expression. Meanwhile, flow cytometry results confirmed a high rate of apoptosis in malignant Human foreskin fibroblasts treated with Botox-A loaded exosome. Conclusion: The findings of this study indicate that exosomal lncRNA H19 could be a diagnostic marker for Breast Cancer and these Breast cancer exosomes can induce malignant phenotype in fibroblasts and turn them into CAFs. Botox-A could be toxic for both normal fibroblasts and CAFs, inducing apoptosis and suppressing cell proliferation among them. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 0890-8508 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0890850824000598; https://doaj.org/toc/0890-8508 |
| DOI: | 10.1016/j.mcp.2024.102007 |
| Access URL: | https://doaj.org/article/4906326b272a4fbdb2924e18b8ba7743 |
| Accession Number: | edsdoj.4906326b272a4fbdb2924e18b8ba7743 |
| Database: | Directory of Open Access Journals |
| ISSN: | 08908508 |
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| DOI: | 10.1016/j.mcp.2024.102007 |
| Published in: | Molecular and Cellular Probes |
| Language: | English |