PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets
Objective(s): Cancer stem cells (CSCs) have powerful self-renewal ability and tumor recurrence. Pancreatic ductal adenocarcinoma is a malignancy with high mortality rate and ˃5% survival. Silybin has anticancer and hepatoprotective properties. We loaded silybin in PEG400-OA (SPNs) and evaluated its...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2021-04-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_17742_9da335ff75b8c39badf5c1d7ebf88fdc.pdf |
| _version_ | 1818900195517136896 |
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| author | Fatemeh Tehrani Najmeh Ranji Fatemeh Kouhkan Simzar Hosseinzadeh |
| author_facet | Fatemeh Tehrani Najmeh Ranji Fatemeh Kouhkan Simzar Hosseinzadeh |
| author_sort | Fatemeh Tehrani |
| collection | DOAJ |
| description | Objective(s): Cancer stem cells (CSCs) have powerful self-renewal ability and tumor recurrence. Pancreatic ductal adenocarcinoma is a malignancy with high mortality rate and ˃5% survival. Silybin has anticancer and hepatoprotective properties. We loaded silybin in PEG400-OA (SPNs) and evaluated its cytotoxic effects on PANC-1 cells and PANC-1 CSCs. Materials and Methods: Spheroids from PANC-1 cells were obtained by the hanging drop method. Anti-proliferative and apoptotic functions of SPNs were evaluated in spheroids and non-spheroids with MTT, DNA fragmentation, PI and PI/AnnexinV assays. The expression of CD markers was assessed with flow cytometry. QRT-PCR was used to evaluate the expression of some miRNAs and targets. Results: IC50 of SPNs was identified to be 50 µg/ml, 45 µg/ml, and 42µg/ml, respectively after 24 hr, 48 hr, and 72 hr in PANC-1 treated cells. PI staining and PI/AnnexinV assay showed that ~20%, ~60%, and ~80%, of cells treated with 30, 50, and 60 µg/ml of SPNs were in sub-G1 and apoptosis phase, respectively. DNA degradation was confirmed after SPNS stimulation. CD24, CD44, and CD133 expression decreased after SPNs treatment both in PANC-1 spheroid cells and PANC-1 cancer cell line. Under-expression of onco-miRs (miR-21, miR-155, and miR-221), over-expression of several apoptotic potential targets of oncomiRs (Bax, Casp-9, and P53), over-expression of tumor suppressive-miRs (let-7b, miR-34a, and miR-126), and under-expression of Bcl-2 was found in SPNs-treated cells. Conclusion: We suggest that silybin encapsulated in polymersomes (SPNs) may be useful as a complementary agent for destroying both pancreatic cancer cells and pancreatic CSCs along with chemotherapeutic agents. |
| first_indexed | 2024-12-19T20:00:00Z |
| format | Article |
| id | doaj.art-f42c5259e0df486baf218ac7fc69e6fd |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-19T20:00:00Z |
| publishDate | 2021-04-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-f42c5259e0df486baf218ac7fc69e6fd2022-12-21T20:07:42ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742021-04-0124451452310.22038/ijbms.2021.54001.1213617742PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targetsFatemeh Tehrani0Najmeh Ranji1Fatemeh Kouhkan2Simzar Hosseinzadeh3Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, IranDepartment of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, IranDepartment of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, IranDepartment of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, IranObjective(s): Cancer stem cells (CSCs) have powerful self-renewal ability and tumor recurrence. Pancreatic ductal adenocarcinoma is a malignancy with high mortality rate and ˃5% survival. Silybin has anticancer and hepatoprotective properties. We loaded silybin in PEG400-OA (SPNs) and evaluated its cytotoxic effects on PANC-1 cells and PANC-1 CSCs. Materials and Methods: Spheroids from PANC-1 cells were obtained by the hanging drop method. Anti-proliferative and apoptotic functions of SPNs were evaluated in spheroids and non-spheroids with MTT, DNA fragmentation, PI and PI/AnnexinV assays. The expression of CD markers was assessed with flow cytometry. QRT-PCR was used to evaluate the expression of some miRNAs and targets. Results: IC50 of SPNs was identified to be 50 µg/ml, 45 µg/ml, and 42µg/ml, respectively after 24 hr, 48 hr, and 72 hr in PANC-1 treated cells. PI staining and PI/AnnexinV assay showed that ~20%, ~60%, and ~80%, of cells treated with 30, 50, and 60 µg/ml of SPNs were in sub-G1 and apoptosis phase, respectively. DNA degradation was confirmed after SPNS stimulation. CD24, CD44, and CD133 expression decreased after SPNs treatment both in PANC-1 spheroid cells and PANC-1 cancer cell line. Under-expression of onco-miRs (miR-21, miR-155, and miR-221), over-expression of several apoptotic potential targets of oncomiRs (Bax, Casp-9, and P53), over-expression of tumor suppressive-miRs (let-7b, miR-34a, and miR-126), and under-expression of Bcl-2 was found in SPNs-treated cells. Conclusion: We suggest that silybin encapsulated in polymersomes (SPNs) may be useful as a complementary agent for destroying both pancreatic cancer cells and pancreatic CSCs along with chemotherapeutic agents.https://ijbms.mums.ac.ir/article_17742_9da335ff75b8c39badf5c1d7ebf88fdc.pdfcancer stem cellmirnapancreatic cancerpolymersomesilybin |
| spellingShingle | Fatemeh Tehrani Najmeh Ranji Fatemeh Kouhkan Simzar Hosseinzadeh PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets Iranian Journal of Basic Medical Sciences cancer stem cell mirna pancreatic cancer polymersome silybin |
| title | PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets |
| title_full | PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets |
| title_fullStr | PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets |
| title_full_unstemmed | PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets |
| title_short | PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets |
| title_sort | panc 1 cancer stem like cell death with silybin encapsulated in polymersomes and deregulation of stemness related mirnas and their potential targets |
| topic | cancer stem cell mirna pancreatic cancer polymersome silybin |
| url | https://ijbms.mums.ac.ir/article_17742_9da335ff75b8c39badf5c1d7ebf88fdc.pdf |
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