Zhang C et al. - Avicin D, a natural triterpenoid saponin selectively induced apoptosis, inhibited STAT-3 activation, and decreased apoptosis inhibitors (bcl-2 and survivin) in cutaneous T-cell lymphomas (CTCL) cell lines and SS patients' Sézary cells. These findings underlie the therapeutic potential of avicin D in patients with SS. Methods
It has been demonstrated that Avicin D inhibits cell growth and induces apoptosis in transformed tumor cell lines and mouse skin carcinogenesis models in vivo
This study was undertaken to investigate the anti-tumor effects of avicin D in CTCL
3 CTCL cell lines and Sézary cells from 3 Sézary syndrome (SS) pts with normal CD4+ and activated CD4+ T cells from 3 healthy donors were used for comparison
Results
Avicin D at 0.5–5 μg ml-1 induced apoptosis in a time- and dose-dependent manner in 3 cell lines at 24 and 48 hrs
Avicin D at 0.5–5 μg ml-1 for 48 hrs caused more apoptosis in patients' Sézary cells than in healthy donors' CD4+ T cells and activated CD4+ T cells
The general caspase inhibitor Z-VAD-FMK and caspase-3 inhibitor Z-DEVD-FMK decreased avicin D-induced apoptosis in CTCL cells
Caspase-3 was activated and poly (ADP-ribose) polymerase was cleaved after avicin D treatment
Avicin D did not change the expression of STAT-3 but decreased p-STAT-3 protein levels in all 3 cell lines and 2 patients' Sézary cells
Avicin D also decreased expression of the inhibitor of apoptosis protein survivin, the anti-apoptotic protein bcl-2, but not the pro-apoptotic protein bax in these CTCL cells
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