PT  - JOURNAL ARTICLE
AU  - NAOKO KUNAMI
AU  - HIROO KATSUYA
AU  - RUMIKO NOGAMI
AU  - KENJI ISHITSUKA
AU  - KAZUO TAMURA
TI  - Promise of Combining a Bcl-2 Family Inhibitor with Bortezomib or SAHA for Adult T-cell Leukemia/Lymphoma
DP  - 2014 Oct 01
TA  - Anticancer Research
PG  - 5287--5294
VI  - 34
IP  - 10
4099  - http://ar.iiarjournals.org/content/34/10/5287.short
4100  - http://ar.iiarjournals.org/content/34/10/5287.full
SO  - Anticancer Res2014 Oct 01; 34
AB  - Background: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of peripheral T-lymphocytes and its prognosis still remains very poor. Materials and Methods: The potential of combining the Bcl-2 homology 3 mimetic ABT-737, which blocks Bcl-2, Bcl-XL, and Bcl-w, with either the proteasome inhibitor bortezomib or histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) to inhibit the growth of human T-lymphotropic virus type-I (HTLV-1) infected T-cell lines and its mechanism was further evaluated. Results: ABT-737 synergistically induced apoptosis when combined with either bortezomib or SAHA in HTLV-1 infected T-cell lines and fresh ATL cells. Bortezomib increased the expression of Noxa, which subsequently enhanced the formation of Mcl-1-Noxa complexes, resulting in the functional neutralization of Mcl-1, an inducer of resistance to ABT-737. On the other hand, SAHA reduced the expression of survivin, an anti-apoptotic molecule that confers drug resistance on ATL cells. Conclusion: The combination of ABT-737 with bortezomib or SAHA is promising for the treatment of ATL.