The effect of diiron thiocarbyne complex on tumor cells of different grade
2023
Аутори:
Mihajlović, EkatarinaJelača, Sanja
Biancalana, Lorenzo
Chiaverini, Lorenzo
Mijatović, Sanja
Zacchini, Stefano
Marchetti, Fabio
Maksimović-Ivanić, Danijela
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2023 by the Serbian Associaton for Cancer Research
Метаподаци
Приказ свих података о документуАпстракт:
Background: Iron is an important trace element with a broad range of functions in diverse physiological processes and tightly regulated metabolism. Over the years, numerous studies have indicated that cancer cells exhibit an iron-seeking phenotype, meaning they have higher demands for iron than healthy cells. This feature may serve as a foundation for a new approach to cancer therapy. In order to develop anticancer drug with improved efficacy, higher selectivity and reduced toxicity, a new organo-diiron complex with a bridging thiocarbyne ligand (FeSDAP) was synthesized. Material and Methods: The cytotoxic effect of FeSDAP was investigated on mouse cancer cell lines (B16-F1 low-invasive melanoma, B16-F10 high-invasive melanoma and 4T1 breast cancer), as well as on mouse embryonic fibroblasts (NIH-3T3). For investigation of its mechanism of action, flow cytometry and light microscopy were used. To investigate how 72h long exposure to DMAP in vitro affect the potential of B16-F1 and B16-F10 cells to form tumor in vivo, respective subcutaneous synegenic models in C57BL/6 mice were used. Results and Conclusions: Treatment with FeSDAP decreased viability of all cells after 72 hours, with significantly less potent effect on embryionic fibroblasts compared to cancer cells, suggesting FeSDAP may possess selectivity towards malignant phenotype. Melanoma cells were almost equally sensitive to the treatment, but more sensitive than breast cancer cells, so both B16-F1 and B16-F10 were selected for further comparative investigation. Treatment with FeSDAP inhibited proliferation of melanoma cells and caused substantial change in their morphology, which was even more pronounced when it comes to B16-F10 cells. After microscopic evaluation, it was shown that melanoma cells went into senescence. Prominent morphological change of B16-F10 cells was caused by transdifferentiation into Schwann Cell-Like Cells. Further investigation of tumorigenic potential of treated melanoma cells in mice showed that the average tumor size in the groups that received treated cells was significantly smaller, suggesting that melanoma cells have persistently reduced potential to form tumor after single in vitro treatment with FeSDAP. Ultimately, these results strongly indicate that investigated diiron thiocarbyne complexes may display a promising antitumor potential that will be investigated in more detail.
Кључне речи:
cell transdifferentiation; cellular senescence; iron compounds; melanomaФинансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. Belgrade, Serbia: Serbian Associaton for Cancer Research; 2023. p. 61-2. (Oncology Insights; No. 1).