| 1. |
- Neuzil, J., et al.
(författare)
-
Induction of cancer cell apoptosis by a-tocopheryl succinate : Molecular pathways and structural requirements
- 2001
-
Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 15:2, s. 403-415
-
Tidskriftsartikel (refereegranskat)abstract
- The vitamin E analog a-tocopheryl succinate (a-TOS) can induce apoptosis. We show that the proapoptotic activity of a-TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented a-TOS-triggered apoptosis. More selective effectors indicated that a-TOS reduced PKCa isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCa inhibition in a-TOS-induced apoptosis was confirmed using antisense oligonucleotides or PKCa overexpression. Gain- or loss-of-function bcl-2 mutants implied modulation of bcl-2 activity by PKC/PP2A as a mitochondrial target of a-TOS-induced proapoptotic signals. Structural analogs revealed that a-tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, a-TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.
|
|
| 2. |
- Neuzil, J., et al.
(författare)
-
Mitochondria transmit apoptosis signalling in cardiomyocyte-like cells and isolated hearts exposed to experimental ischemia-reperfusion injury
- 2007
-
Ingår i: Redox report. - 1351-0002 .- 1743-2928. ; 12:3, s. 148-162
-
Tidskriftsartikel (refereegranskat)abstract
- Ischemia-reperfusion (I/R) is a condition leading to serious complications due to death of cardiac myocytes. We used the cardiomyocyte-like cell line H9c2 to study the mechanism underlying cell damage. Exposure of the cells to simulated I/R lead to their apoptosis. Over-expression of Bcl-2 and Bcl-xL protected the cells from apoptosis while over-expression of Bax sensitized them to programmed cell death induction. Mitochondria-targeted coenzyme Q (mitoQ) and superoxide dismutase both inhibited accumulation of reactive oxygen species (ROS) and apoptosis induction. Notably, mtDNA-deficient cells responded to I/R by decreased ROS generation and apoptosis. Using both in situ and in vivo approaches, it was found that apoptosis occurred during reperfusion following ischemia, and recovery was enhanced when hearts from mice were supplemented with mitoQ. In conclusion, I/R results in apoptosis in cultured cardiac myocytes and heart tissue largely via generation of mitochondria-derived superoxide, with ensuing apoptosis during the reperfusion phase. © W. S. Maney & Son Ltd.
|
|
| 3. |
|
|
| 4. |
|
|
