2013 May 11. [Epub ahead of print]
Curcumin targets the AKT–mTOR pathway for uterine leiomyosarcoma tumor
Wong TF, Takeda T, Li B, Tsuiji K, Kondo A, Tadakawa M, Nagase S, Yaegashi
Department of Obstetrics and Gynecology, Tohoku University Graduate School
of Medicine, Sendai, Miyagi, Japan.
Uterine leiomyosarcomas generally do not respond well to standard
chemotherapy. We previously demonstrated that curcumin, the active
ingredient derived from the herb Curcuma longa, inhibits uterine
leiomyosarcoma cells in vitro via the inhibition of the AKT-mammalian
target of rapamycin (mTOR) pathway. As a preclinical investigation, we
performed an in vivo study using female nude mice to confirm the
therapeutic potential of curcumin against uterine leiomyosarcoma.
Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice
to establish subcutaneous tumors. Either vehicle control or 250 mg/kg
curcumin was administered intraperitoneally every day for 14 consecutive
days, and the mice were then killed. The tumors were measured every 2-3
days. The tumors were processed for immunohistochemical analyses to detect
total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and
phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved
PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell
viability of the tumors.
Compared with the control, curcumin reduced uterine leiomyosarcoma tumor
volume and mass significantly with a concordant decrease in mTOR and S6
phosphorylation. However, AKT phosphorylation was not significantly
altered. Cleaved PARP and TUNEL staining increased significantly with
curcumin administration, indicating the induction of apoptosis. There was
no difference in Ki-67 staining between the two groups.
Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by
targeting the AKT-mTOR pathway for inhibition.
[PubMed – as supplied by publisher]