Cellular distribution studies of the nitric oxide-generating antineoplastic prodrug O(2) -(2,4-dinitrophenyl)1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate formulated in Pluronic P123 micelles
© 2013 Royal Pharmaceutical Society..
OBJECTIVE: Nitric oxide (NO) possesses antitumour activity. It induces differentiation and apoptosis in acute myeloid leukaemia (AML) cells. The NO prodrug O(2) -(2,4-dinitrophenyl)1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate, or JS-K, has potent antileukaemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small-cell lung cancer, glioma and liver cancer. Using the Pluronic P123 polymer, we have developed a micelle formulation for JS-K to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells.
METHODS: We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions.
KEY FINDINGS: Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed.
CONCLUSIONS: We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K's antileukaemic properties.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
|---|---|
| Enthalten in: |
The Journal of pharmacy and pharmacology - 65(2013), 9 vom: 24. Sept., Seite 1329-36 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kaur, Imit [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 25.02.2014 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/jphp.12100 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM229857574 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM229857574 | ||
| 003 | DE-627 | ||
| 005 | 20231224083058.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/jphp.12100 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0766.xml |
| 035 | |a (DE-627)NLM229857574 | ||
| 035 | |a (NLM)23927471 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kaur, Imit |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cellular distribution studies of the nitric oxide-generating antineoplastic prodrug O(2) -(2,4-dinitrophenyl)1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate formulated in Pluronic P123 micelles |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.02.2014 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2013 Royal Pharmaceutical Society. | ||
| 520 | |a OBJECTIVE: Nitric oxide (NO) possesses antitumour activity. It induces differentiation and apoptosis in acute myeloid leukaemia (AML) cells. The NO prodrug O(2) -(2,4-dinitrophenyl)1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate, or JS-K, has potent antileukaemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small-cell lung cancer, glioma and liver cancer. Using the Pluronic P123 polymer, we have developed a micelle formulation for JS-K to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells | ||
| 520 | |a METHODS: We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions | ||
| 520 | |a KEY FINDINGS: Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed | ||
| 520 | |a CONCLUSIONS: We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K's antileukaemic properties | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a JS-K | |
| 650 | 4 | |a Pluronic | |
| 650 | 4 | |a leukaemia | |
| 650 | 4 | |a nitric oxide | |
| 650 | 4 | |a poloxamer | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Azo Compounds |2 NLM | |
| 650 | 7 | |a Micelles |2 NLM | |
| 650 | 7 | |a Nitric Oxide Donors |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Prodrugs |2 NLM | |
| 650 | 7 | |a pluronic block copolymer P123 |2 NLM | |
| 650 | 7 | |a 2E9U4Y94DB |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 650 | 7 | |a Poloxalene |2 NLM | |
| 650 | 7 | |a 9003-11-6 |2 NLM | |
| 700 | 1 | |a Terrazas, Moises |e verfasserin |4 aut | |
| 700 | 1 | |a Kosak, Ken M |e verfasserin |4 aut | |
| 700 | 1 | |a Kern, Steven E |e verfasserin |4 aut | |
| 700 | 1 | |a Boucher, Kenneth M |e verfasserin |4 aut | |
| 700 | 1 | |a Shami, Paul J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of pharmacy and pharmacology |d 1949 |g 65(2013), 9 vom: 24. Sept., Seite 1329-36 |w (DE-627)NLM000019046 |x 2042-7158 |7 nnns |
| 773 | 1 | 8 | |g volume:65 |g year:2013 |g number:9 |g day:24 |g month:09 |g pages:1329-36 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/jphp.12100 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 65 |j 2013 |e 9 |b 24 |c 09 |h 1329-36 | ||