دورية أكاديمية
3-AP inhibits the growth of human osteosarcoma by decreasing the activity of the iron-dependent pathway.
| العنوان: | 3-AP inhibits the growth of human osteosarcoma by decreasing the activity of the iron-dependent pathway. |
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| المؤلفون: | Huang S; Department of Orthopedics, Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China., Zhang D; Department of Orthopedics, Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China., Yi X; Department of Orthopedics, Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China., Liu C; Department of Orthopedics, Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China., Jian C; Department of Orthopedics, Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China. chaojian@whu.edu.cn.; Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, People's Republic of China. chaojian@whu.edu.cn., Yu A; Department of Orthopedics, Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China. yuaixi@whu.edu.cn.; Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, People's Republic of China. yuaixi@whu.edu.cn. |
| المصدر: | Medical oncology (Northwood, London, England) [Med Oncol] 2023 Nov 11; Vol. 40 (12), pp. 353. Date of Electronic Publication: 2023 Nov 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: United States NLM ID: 9435512 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-131X (Electronic) Linking ISSN: 13570560 NLM ISO Abbreviation: Med Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2011- : New York : Springer Original Publication: Northwood, Middlesex, England : Science and Technology Letters, c1994- |
| مواضيع طبية MeSH: | Osteosarcoma*/drug therapy , Osteosarcoma*/pathology , Ribonucleotide Reductases*/therapeutic use , Bone Neoplasms*/drug therapy , Bone Neoplasms*/pathology, Humans ; Animals ; Mice ; Iron/therapeutic use ; Mice, Nude ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis |
| مستخلص: | 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) has broad-spectrum antitumor activity. However, its role in osteosarcoma (OS) remains unclear. Therefore, this study explored the effects of 3-AP on OS in vitro and in vivo using three human OS cell lines (MG-63, U2-OS, and 143B) and a nude mice model generated by transplanting 143B cells. The cells and mice were treated with DMSO (control) or gradient concentrations of 3-AP. Then, various assays (e.g., cell counting kit-8, flow cytometry, immunohistochemistry, and western blotting) were performed to assess cell viability and apoptosis levels, as well as γH2A.X (DNA damage correlation), ribonucleotide reductase catalytic subunit M1 and M2 (RRM1 and RRM2, respectively) protein levels (iron-dependent correlation). 3-AP time- and dose-dependably suppressed growth and induced apoptosis in all three OS cell lines, and ferric ammonium citrate (FAC) blocked these effects. Moreover, 3-AP decreased RRM2 and total ribonucleotide reductase (RRM1 plus RRM2) protein expression but significantly increased γH2A.X expression; treatment did not affect RRM1 expression. Again, FAC treatment attenuated these effects. In vivo, the number of apoptotic cells in the tumor slices increased in the 3-AP-treated mice compared to the control mice. 3-AP treatment also decreased Ki-67 and p21 expression, suggesting inhibited OS growth. Furthermore, the expression of RRM1, RRM2, and transferrin receptor protein 1 (i.e., Tfr1) indicated that 3-AP inhibited OS growth via an iron-dependent pathway. In conclusion, 3-AP exhibits anticancer activity in OS by decreasing the activity of iron-dependent pathways, which could be a promising therapeutic strategy for OS. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
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| معلومات مُعتمدة: | LJ20200405 Hubei Province Medical Leading Talent Project; PTXM2021020 Hubei Technological Innovation Special Fund |
| فهرسة مساهمة: | Keywords: 3-aminopyridine-2-carboxaldehyde thiosemicarbazone; Apoptosis; Iron chelator; Osteosarcoma; Proliferation; Ribonucleotide reductase |
| المشرفين على المادة: | 143621-35-6 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) E1UOL152H7 (Iron) EC 1.17.4.- (Ribonucleotide Reductases) |
| تواريخ الأحداث: | Date Created: 20231111 Date Completed: 20231113 Latest Revision: 20231120 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1007/s12032-023-02215-2 |
| PMID: | 37952032 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1559-131X |
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| DOI: | 10.1007/s12032-023-02215-2 |