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- Olsson, A R (author)
Mechanism of action for N-substituted benzamide-induced apoptosis.
- Article/chapterEnglish2002
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- 2002
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- LIBRIS-ID:oai:lup.lub.lu.se:85487805-eb78-455a-a249-141a60681091
- https://lup.lub.lu.se/record/107655URI
- https://doi.org/10.1038/sj/bjc/6600136DOI
Supplementary language notes
- Language:English
- Summary in:English
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Notes
- We have analysed the mechanism of action for induction of apoptosis by N-substituted benzamides using declopramide as a lead compound. We show here that declopramide at doses above 250 microM in the mouse 70Z/3 pre-B cell line or in the human promyeolocytic cancer cell line HL60 induced cytochrome c release into the cytosol and caspase-9 activation. The broad spectrum caspase inhibitor zVADfmk and caspase-9 inhibitor zLEDHfmk inhibited apoptosis and improved cell viability when administrated to cells 1 h before exposure to declopramide, whereas the caspase-8 inhibitor zIEDHfmk had less effect. Also, the over expression of Bcl-2 by transfection in 70Z/3 cells inhibited declopramide-induced apoptosis. Prior to the induction of apoptosis, a G(2)/M cell cycle block was induced by declopramide. The cell cycle block was also observed in the presence of broad spectrum caspase inhibitor zVADfmk and in a transfectant expressing high levels of Bcl-2. Furthermore, while p53 was induced in 70Z/3 cells by declopramide, neither the apoptotic mechanism nor the G(2)/M cell cycle block were dependent on p53 activation since both effects were also seen in p53 deficient HL60 cells after addition of declopramide.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
- G2 Phase : drug effects
- HL-60 Cells
- Metoclopramide : pharmacology
- Human
- Mitosis : drug effects
- Procainamide : analogs & derivatives
- Procainamide : pharmacology
- Protein p53 : physiology
- Benzamides : pharmacology
- Proto-Oncogene Proteins c-bcl-2 : physiology
- Cytochrome c : secretion
- Enzyme Activation
- Apoptosis : drug effects
- Caspases : metabolism
Added entries (persons, corporate bodies, meetings, titles ...)
- Lindgren, HannaLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups(Swepub:lu)immu-hli (author)
- Pero, RonaldLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups(Swepub:lu)wbl-rpe (author)
- Leanderson, TomasLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups(Swepub:lu)immu-tle (author)
- ImmunologiForskargrupper vid Lunds universitet (creator_code:org_t)
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- In:British Journal of Cancer86:6, s. 971-9781532-1827
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