The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model
Само за регистроване кориснике
2019
Аутори
Draca, DijanaMijatović, Sanja
Krajnović, Tamara
Bogdanović Pristov, Jelena
Dukic, Tatjana
Kaluderović, Goran N.
Wessjohann, Ludger A.
Maksimović-Ivanić, Danijela
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxeltreated animals Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic a...ctivity and were functionally and phenotypically recognized as Ml. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward Ml, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.
Кључне речи:
Tubulysin / Phosphatidylserine / Macrophage polarization / Cancer / ApoptosisИзвор:
Experimental Cell Research, 2019, 380, 2, 159-170Издавач:
- Elsevier Inc, San Diego
Финансирање / пројекти:
- Молекуларни механизми физиолошке и фармаколошке контроле инфламације и канцера (RS-MESTD-Basic Research (BR or ON)-173013)
- Leibniz Institute of Plant Biochemistry, Halle
- German Academic Exchange Service (DAAD)Deutscher Akademischer Austausch Dienst (DAAD)
DOI: 10.1016/j.yexcr.2019.04.028
ISSN: 0014-4827
PubMed: 31042500
WoS: 000469307600006
Scopus: 2-s2.0-85065046067
Институција/група
Institut za multidisciplinarna istraživanjaTY - JOUR AU - Draca, Dijana AU - Mijatović, Sanja AU - Krajnović, Tamara AU - Bogdanović Pristov, Jelena AU - Dukic, Tatjana AU - Kaluderović, Goran N. AU - Wessjohann, Ludger A. AU - Maksimović-Ivanić, Danijela PY - 2019 UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/1228 AB - Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxeltreated animals Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as Ml. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward Ml, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects. PB - Elsevier Inc, San Diego T2 - Experimental Cell Research T1 - The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model EP - 170 IS - 2 SP - 159 VL - 380 DO - 10.1016/j.yexcr.2019.04.028 ER -
@article{ author = "Draca, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Dukic, Tatjana and Kaluderović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela", year = "2019", abstract = "Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxeltreated animals Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as Ml. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward Ml, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.", publisher = "Elsevier Inc, San Diego", journal = "Experimental Cell Research", title = "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model", pages = "170-159", number = "2", volume = "380", doi = "10.1016/j.yexcr.2019.04.028" }
Draca, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Dukic, T., Kaluderović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2019). The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research Elsevier Inc, San Diego., 380(2), 159-170. https://doi.org/10.1016/j.yexcr.2019.04.028
Draca D, Mijatović S, Krajnović T, Bogdanović Pristov J, Dukic T, Kaluderović GN, Wessjohann LA, Maksimović-Ivanić D. The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research. 2019;380(2):159-170. doi:10.1016/j.yexcr.2019.04.028 .
Draca, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Dukic, Tatjana, Kaluderović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model" in Experimental Cell Research, 380, no. 2 (2019):159-170, https://doi.org/10.1016/j.yexcr.2019.04.028 . .