The British journal of dermatology · 2008
Antitumour effects in mycosis fungoides of the immunomodulatory, tellurium-based compound, AS101.
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Frei G M, Kremer M, Hanschmann K-M, Krause S, Albeck M, Sredni B, Schnierle B S
Аннотация
BACKGROUND: The immunomodulator AS101 [ammonium trichloro (dioxoethylene-O,O') tellurate], a nontoxic tellurium (IV) compound, has antitumoral effects which were demonstrated in several preclinical and clinical studies.
OBJECTIVES: To investigate the antitumour activity of AS101 on cutaneous T-cell lymphoma (CTCL), of which mycosis fungoides (MF) is the most frequent disease variant.
METHODS: We used a newly established mouse xenograft model for MF to test the effect of AS101 in vivo and analysed apoptosis induction in vitro.
RESULTS: When injected intratumorally, AS101 delayed tumour growth in a dose-dependent manner. In vitro, AS101 induced a dose-dependent G2/M arrest in the CTCL cell lines Hut78 and MyLa. Moreover, higher concentrations of AS101 induced apoptosis in MyLa cells. Programmed cell death was associated with the loss of mitochondrial transmembrane potential and activation of caspase 9 and caspase 3. AS101 also elevated intracellular reactive oxygen species (ROS) production; the antioxidant, Mn superoxide dismutase, significantly reduced the degree of apoptosis, suggesting that ROS play a key role in apoptosis induction.
CONCLUSIONS: These findings indicate that AS101 may be a promising antitumour drug for CTCL.
OBJECTIVES: To investigate the antitumour activity of AS101 on cutaneous T-cell lymphoma (CTCL), of which mycosis fungoides (MF) is the most frequent disease variant.
METHODS: We used a newly established mouse xenograft model for MF to test the effect of AS101 in vivo and analysed apoptosis induction in vitro.
RESULTS: When injected intratumorally, AS101 delayed tumour growth in a dose-dependent manner. In vitro, AS101 induced a dose-dependent G2/M arrest in the CTCL cell lines Hut78 and MyLa. Moreover, higher concentrations of AS101 induced apoptosis in MyLa cells. Programmed cell death was associated with the loss of mitochondrial transmembrane potential and activation of caspase 9 and caspase 3. AS101 also elevated intracellular reactive oxygen species (ROS) production; the antioxidant, Mn superoxide dismutase, significantly reduced the degree of apoptosis, suggesting that ROS play a key role in apoptosis induction.
CONCLUSIONS: These findings indicate that AS101 may be a promising antitumour drug for CTCL.