Journal Article

Se-Methylselenocysteine induces apoptosis through caspase activation in HL-60 cells

Taeho Kim, Uhee Jung, Dae-Yeon Cho and An-Sik Chung

in Carcinogenesis

Volume 22, issue 4, pages 559-565
Published in print April 2001 | ISSN: 0143-3334
Published online April 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.4.559
Se-Methylselenocysteine induces apoptosis through caspase activation in HL-60 cells

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Apoptosis, a programmed process of cell suicide, has been proposed as the most plausible mechanism for the chemopreventive activities of selenocompounds. In our study, we found that Se-methylselenocysteine (MSC) induced apoptosis through caspase activation in human promyelocytic leukemia (HL-60) cells. Measurements of cytotoxicity, DNA fragmentation and apoptotic morphology revealed that MSC was more efficient at inducing apoptosis than selenite, but was less toxic. Moreover, MSC increased both the apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 activity, whereas selenite did not. We next examined whether caspases and serine proteases are required for the apoptotic induction by MSC. A general caspase inhibitor, z-VAD-fmk, dramatically decreased cytotoxicity in MSC-treated HL-60 cells and several other apoptotic features, such as, caspase-3 activation, the apoptotic DNA ladder, TUNEL-positive staining and the DNA double-strand break. Interestingly, a general serine protease inhibitor, AAPV-cmk, also effectively inhibited MSC-mediated cytotoxicity and apoptosis. These results demonstrate that MSC is a selenocompound that efficiently induces apoptosis in leukemia cells and that proteolytic machinery, in particular caspase-3, is necessary for MSC-induced apoptosis. On the other hand, selenite-induced cell death could be derived from necrosis rather than apoptosis, since selenite did not significantly induce several apoptotic phenomena, including the activation of caspase-3.

Keywords: AAPV-cmk, Ala-Ala-Pro-Val-chloromethylketone; DEVD-pNA, Asp-Glu-Val-Asp-p-nitroanilide; LDH, lactate dehydrogenase; MSC, Se-methylselenocysteine; PARP, poly(ADP-ribose) polymerase; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; z-VAD-fmk, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone.

Journal Article.  5484 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.