A novel therapeutic potential for
acute promyelocytic leukemia using
arsenic trioxide (
As(2) O(3) ) has been reported. Recent in vitro studies demonstrated that
As(2) O(3) effectively inhibits the growth of some cell lines derived from patients with
malignant lymphoma,
chronic lymphocytic leukemia and
multiple myeloma.
Adult T-cell leukemia (ATL) is an aggressive
neoplasm of mature T-cell origin caused by human
T-cell leukemia virus type-I (HTLV-I) the prognosis of which still remains very poor. A possible role of
As(2) O(3) for the treatment of ATL is demonstrated from evidence that
As(2) O(3) significantly inhibits the growth of HTLV-I infected T-cell lines and induces apoptosis in fresh ATL cells at clinically achievable concentration of the agent. The growth inhibition of
As(2) O(3) treated HTLV-I infected T-cell lines was induced by both apoptosis and G(1) phase accumulation. Cleaved bcl-2
protein and an enhanced expression of
bak protein in the cells were coincidentally observed during
As(2) O(3) treatment. A broad spectrum
caspase inhibitor, z-Val-Ala-DL-Asp-fluoromethylketone inhibited the apoptosis induced by
As(2) O(3). Increased expression of p53, Cip1/p21 and Kip1/p27, and dephosphorylation of
retinoblastoma protein (pRb) were detected in the
As(2) O(3) treated cells. In conclusion,
As(2) O(3) might become a new therapeutic tool in the treatment of ATL as
As(2) O(3) induces apoptosis by destruction of the bcl-2
protein and enhancement of the
bak protein production proceeding to activate
caspases, and also induces G(1) phase accumulation by enhancement of p53, Cip1/p21, Kip1/p27 and dephosphorylation of pRb to HTLV-I infected T-cell lines.