Ispitivanje citotoksične aktivnosti aminokiselinskih estara vitamina E na ćelijama tumora dojke i pluća
Cytotoxic activity of amino acid esters of vitamin E against breast and lung cancer cell lines
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U velikom broju studija pokazana je antitumorska aktivnost prirodnih izomera
vitamina E, a naročito njihovih polusintetskih derivata. Cilj ove studije je bio ispitivanje
citotoksične aktivnosti estara α‐tokoferola sa aminokiselinama lizinom, prolinom,
glutaminom, asparaginom i estara γ‐tokotrienola sa lizinom, prolinom i glutaminom na
MCF7 i MDA‐MB 231 ćelijskim linijama tumora dojke i A549 ćelijskoj liniji tumora
pluća. Sve ćelijske linije tretirane su koncentracijama ispitivanih jedinjenja u opsegu
0,62‐50 μM u toku 48 sati. Preživljavanje ćelija nakon tretmana ispitivanim
jedinjenjima je određeno MTT‐testom. Najveći uticaj na preživljavanje malignih ćelija
su imali α‐tokoferil lizin, α‐tokoferil asparagin u formi nitrila i γ‐tokotrienil lizin. α‐
Tokoferil lizin je ispoljio snažnu antitumorsku aktivnost na A549 (IC50=10,6 μM) i MCF7
(IC50=8,6 μM) ćelijama, dok je γ‐tokotrienil lizin je jedini od ispitivanih jedinjenja koji je
ispoljio aktivnost na sve tri maligne ćelijske... linije, sa IC50 vrednostima 20,6 μM (MCF7),
28,6 μM (MDA‐MB‐231) i 19 μM (A549). Asparaginski estar α‐tokoferola u formi nitrila
je je doveo do snažne inhibicije preživljavanja MDA‐MB‐231 ćelija (IC50=9,2 μM) koje se
odlikuju višestrukom rezistencijom na lekove koji se koriste u terapiji tumora dojke.
Ispitivana jedinjenja nisu ispoljila toksičnost ka MRC‐5 zdravoj ćelijskoj liniji fetalnih
fibroblasta pluća.
Zahvaljujući pokazanoj in vitro citotoksičnoj aktivnosti i selektivnosti za maligne
ćelije, aminokiselinski estri α‐tokoferola i γ‐tokotrienola predstavljaju dobre kandidate
za buduća in vivo ispitivanja.
In recent studies, the antitumor activity of vitamin E derivatives has been
demonstrated. The aim of this study was to investigate the cytotoxic activity of α‐
tocopherol esters with amino acids lysine, proline, glutamine, asparagine and γ‐
tocotrienol esters with lysine, proline and glutamine on MCF7 and MDA‐MB 231 breast
cancer cell lines and A549 lung cancer cell line. All cell lines were treated with
concentrations of the test compounds in the range of 0.62‐50 μM for 48 hours. Cell
survival after treatment with the investigated compounds was determined by MTT test.
The greatest influence on the survival of malignant cells was observed with α‐
tocopheryl lysine, α‐tocopheryl asparagine in the form of nitrile and γ‐tocotrienyl
lysine. α‐Tocopheryl lysine exhibited strong cytotoxic activity on A549 (IC50 = 10.6 μM)
and MCF7 (IC50 = 8.6 μM) cells, while γ‐tocotrienyl lysine is the only compound that
exhibited activity on all three cancer cell lines, with IC50 values of 20.6 ...μM (MCF7),
28.6μM (MDA‐MB‐231) and 19 μM (A549). The α‐tocopheryl asparagine nitrile led to a
strong inhibition of the survival of MDA‐MB‐231 cells (IC50 =9.2 μM) that are
characterized by multiple resistance to drugs used for treatment of breast cancer. All
investigated compounds did not exhibit toxicity to normal MRC‐5 cell line of the fetal
fibroblasts of the lungs.
Based on the shown in vitro cytotoxic activity and selectivity for tumor cells, α‐
tocopherol and γ‐tocotrienol amino acid esters represent promising candidates for
future in vivo studies.
Source:
Arhiv za farmaciju, 2018, 68, 3, 391-392Publisher:
- Savez farmaceutskih udruženja Srbije (SFUS)
Funding / projects:
Note:
- VII Kongres farmaceuta Srbije sa međunarodnim učešćem Zajedno stvaramo budućnost farmacije Beograd, 10-14. oktobar 2018
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PharmacyTY - CONF AU - Gagić, Žarko AU - Srdić-Rajić, Tatjana AU - Nikolić, Katarina AU - Agbaba, Danica PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4877 AB - U velikom broju studija pokazana je antitumorska aktivnost prirodnih izomera vitamina E, a naročito njihovih polusintetskih derivata. Cilj ove studije je bio ispitivanje citotoksične aktivnosti estara α‐tokoferola sa aminokiselinama lizinom, prolinom, glutaminom, asparaginom i estara γ‐tokotrienola sa lizinom, prolinom i glutaminom na MCF7 i MDA‐MB 231 ćelijskim linijama tumora dojke i A549 ćelijskoj liniji tumora pluća. Sve ćelijske linije tretirane su koncentracijama ispitivanih jedinjenja u opsegu 0,62‐50 μM u toku 48 sati. Preživljavanje ćelija nakon tretmana ispitivanim jedinjenjima je određeno MTT‐testom. Najveći uticaj na preživljavanje malignih ćelija su imali α‐tokoferil lizin, α‐tokoferil asparagin u formi nitrila i γ‐tokotrienil lizin. α‐ Tokoferil lizin je ispoljio snažnu antitumorsku aktivnost na A549 (IC50=10,6 μM) i MCF7 (IC50=8,6 μM) ćelijama, dok je γ‐tokotrienil lizin je jedini od ispitivanih jedinjenja koji je ispoljio aktivnost na sve tri maligne ćelijske linije, sa IC50 vrednostima 20,6 μM (MCF7), 28,6 μM (MDA‐MB‐231) i 19 μM (A549). Asparaginski estar α‐tokoferola u formi nitrila je je doveo do snažne inhibicije preživljavanja MDA‐MB‐231 ćelija (IC50=9,2 μM) koje se odlikuju višestrukom rezistencijom na lekove koji se koriste u terapiji tumora dojke. Ispitivana jedinjenja nisu ispoljila toksičnost ka MRC‐5 zdravoj ćelijskoj liniji fetalnih fibroblasta pluća. Zahvaljujući pokazanoj in vitro citotoksičnoj aktivnosti i selektivnosti za maligne ćelije, aminokiselinski estri α‐tokoferola i γ‐tokotrienola predstavljaju dobre kandidate za buduća in vivo ispitivanja. AB - In recent studies, the antitumor activity of vitamin E derivatives has been demonstrated. The aim of this study was to investigate the cytotoxic activity of α‐ tocopherol esters with amino acids lysine, proline, glutamine, asparagine and γ‐ tocotrienol esters with lysine, proline and glutamine on MCF7 and MDA‐MB 231 breast cancer cell lines and A549 lung cancer cell line. All cell lines were treated with concentrations of the test compounds in the range of 0.62‐50 μM for 48 hours. Cell survival after treatment with the investigated compounds was determined by MTT test. The greatest influence on the survival of malignant cells was observed with α‐ tocopheryl lysine, α‐tocopheryl asparagine in the form of nitrile and γ‐tocotrienyl lysine. α‐Tocopheryl lysine exhibited strong cytotoxic activity on A549 (IC50 = 10.6 μM) and MCF7 (IC50 = 8.6 μM) cells, while γ‐tocotrienyl lysine is the only compound that exhibited activity on all three cancer cell lines, with IC50 values of 20.6 μM (MCF7), 28.6μM (MDA‐MB‐231) and 19 μM (A549). The α‐tocopheryl asparagine nitrile led to a strong inhibition of the survival of MDA‐MB‐231 cells (IC50 =9.2 μM) that are characterized by multiple resistance to drugs used for treatment of breast cancer. All investigated compounds did not exhibit toxicity to normal MRC‐5 cell line of the fetal fibroblasts of the lungs. Based on the shown in vitro cytotoxic activity and selectivity for tumor cells, α‐ tocopherol and γ‐tocotrienol amino acid esters represent promising candidates for future in vivo studies. PB - Savez farmaceutskih udruženja Srbije (SFUS) C3 - Arhiv za farmaciju T1 - Ispitivanje citotoksične aktivnosti aminokiselinskih estara vitamina E na ćelijama tumora dojke i pluća T1 - Cytotoxic activity of amino acid esters of vitamin E against breast and lung cancer cell lines VL - 68 IS - 3 SP - 391 EP - 392 UR - https://hdl.handle.net/21.15107/rcub_farfar_4877 ER -
@conference{ author = "Gagić, Žarko and Srdić-Rajić, Tatjana and Nikolić, Katarina and Agbaba, Danica", year = "2018", abstract = "U velikom broju studija pokazana je antitumorska aktivnost prirodnih izomera vitamina E, a naročito njihovih polusintetskih derivata. Cilj ove studije je bio ispitivanje citotoksične aktivnosti estara α‐tokoferola sa aminokiselinama lizinom, prolinom, glutaminom, asparaginom i estara γ‐tokotrienola sa lizinom, prolinom i glutaminom na MCF7 i MDA‐MB 231 ćelijskim linijama tumora dojke i A549 ćelijskoj liniji tumora pluća. Sve ćelijske linije tretirane su koncentracijama ispitivanih jedinjenja u opsegu 0,62‐50 μM u toku 48 sati. Preživljavanje ćelija nakon tretmana ispitivanim jedinjenjima je određeno MTT‐testom. Najveći uticaj na preživljavanje malignih ćelija su imali α‐tokoferil lizin, α‐tokoferil asparagin u formi nitrila i γ‐tokotrienil lizin. α‐ Tokoferil lizin je ispoljio snažnu antitumorsku aktivnost na A549 (IC50=10,6 μM) i MCF7 (IC50=8,6 μM) ćelijama, dok je γ‐tokotrienil lizin je jedini od ispitivanih jedinjenja koji je ispoljio aktivnost na sve tri maligne ćelijske linije, sa IC50 vrednostima 20,6 μM (MCF7), 28,6 μM (MDA‐MB‐231) i 19 μM (A549). Asparaginski estar α‐tokoferola u formi nitrila je je doveo do snažne inhibicije preživljavanja MDA‐MB‐231 ćelija (IC50=9,2 μM) koje se odlikuju višestrukom rezistencijom na lekove koji se koriste u terapiji tumora dojke. Ispitivana jedinjenja nisu ispoljila toksičnost ka MRC‐5 zdravoj ćelijskoj liniji fetalnih fibroblasta pluća. Zahvaljujući pokazanoj in vitro citotoksičnoj aktivnosti i selektivnosti za maligne ćelije, aminokiselinski estri α‐tokoferola i γ‐tokotrienola predstavljaju dobre kandidate za buduća in vivo ispitivanja., In recent studies, the antitumor activity of vitamin E derivatives has been demonstrated. The aim of this study was to investigate the cytotoxic activity of α‐ tocopherol esters with amino acids lysine, proline, glutamine, asparagine and γ‐ tocotrienol esters with lysine, proline and glutamine on MCF7 and MDA‐MB 231 breast cancer cell lines and A549 lung cancer cell line. All cell lines were treated with concentrations of the test compounds in the range of 0.62‐50 μM for 48 hours. Cell survival after treatment with the investigated compounds was determined by MTT test. The greatest influence on the survival of malignant cells was observed with α‐ tocopheryl lysine, α‐tocopheryl asparagine in the form of nitrile and γ‐tocotrienyl lysine. α‐Tocopheryl lysine exhibited strong cytotoxic activity on A549 (IC50 = 10.6 μM) and MCF7 (IC50 = 8.6 μM) cells, while γ‐tocotrienyl lysine is the only compound that exhibited activity on all three cancer cell lines, with IC50 values of 20.6 μM (MCF7), 28.6μM (MDA‐MB‐231) and 19 μM (A549). The α‐tocopheryl asparagine nitrile led to a strong inhibition of the survival of MDA‐MB‐231 cells (IC50 =9.2 μM) that are characterized by multiple resistance to drugs used for treatment of breast cancer. All investigated compounds did not exhibit toxicity to normal MRC‐5 cell line of the fetal fibroblasts of the lungs. Based on the shown in vitro cytotoxic activity and selectivity for tumor cells, α‐ tocopherol and γ‐tocotrienol amino acid esters represent promising candidates for future in vivo studies.", publisher = "Savez farmaceutskih udruženja Srbije (SFUS)", journal = "Arhiv za farmaciju", title = "Ispitivanje citotoksične aktivnosti aminokiselinskih estara vitamina E na ćelijama tumora dojke i pluća, Cytotoxic activity of amino acid esters of vitamin E against breast and lung cancer cell lines", volume = "68", number = "3", pages = "391-392", url = "https://hdl.handle.net/21.15107/rcub_farfar_4877" }
Gagić, Ž., Srdić-Rajić, T., Nikolić, K.,& Agbaba, D.. (2018). Ispitivanje citotoksične aktivnosti aminokiselinskih estara vitamina E na ćelijama tumora dojke i pluća. in Arhiv za farmaciju Savez farmaceutskih udruženja Srbije (SFUS)., 68(3), 391-392. https://hdl.handle.net/21.15107/rcub_farfar_4877
Gagić Ž, Srdić-Rajić T, Nikolić K, Agbaba D. Ispitivanje citotoksične aktivnosti aminokiselinskih estara vitamina E na ćelijama tumora dojke i pluća. in Arhiv za farmaciju. 2018;68(3):391-392. https://hdl.handle.net/21.15107/rcub_farfar_4877 .
Gagić, Žarko, Srdić-Rajić, Tatjana, Nikolić, Katarina, Agbaba, Danica, "Ispitivanje citotoksične aktivnosti aminokiselinskih estara vitamina E na ćelijama tumora dojke i pluća" in Arhiv za farmaciju, 68, no. 3 (2018):391-392, https://hdl.handle.net/21.15107/rcub_farfar_4877 .