کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3943026 1254066 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی زنان، زایمان و بهداشت زنان
پیش نمایش صفحه اول مقاله
Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition
چکیده انگلیسی

ObjectiveUterine leiomyosarcoma generally has an unfavorable response to standard chemotherapy. The loss of PTEN which results in constitutive AKT-mTOR activation causes an increase in leiomyosarcoma formation in mice. The active ingredient derived from the herb Curcuma longa, curcumin, shows antitumor properties in a variety of cancer cell lines by altering a number of oncogenic pathways. To explore the possibility of curcumin as an alternative to standard chemotherapy, we decided to investigate curcumin's antitumor effect on uterine leiomyosarcoma cells.MethodsHuman leiomyosarcoma cell lines, SKN and SK-UT-1, were cultured for in vitro experiments. Rapamycin or curcumin was added in different doses and their effect on cell growth was detected by MTS assay. The influence of rapamycin or curcumin on AKT, mTOR, p70S6 and S6 phosphorylation and protein expression was detected by Western Blotting. The ability of rapamycin or curcumin to induce apoptosis was determined by Western blotting using cleaved-PARP specific antibody, Caspase-3 activity assay and TUNEL assay.ResultsBoth rapamycin and curcumin significantly reduced SKN cell proliferation. Curcumin inhibited mTOR, p70S6 and S6 phosphorylation similar with rapamycin. Cleaved PARP, caspase-3 activity and DNA fragmentation increased proportional with curcumin concentration. At a high concentration, curcumin significantly induced apoptosis in SKN cells, but not rapamycin.ConclusionsCurcumin inhibited uterine leiomyosarcoma cells' growth by targeting the AKT-mTOR pathway for inhibition. However, rapamycin, a specific mTOR inhibitor, did not induce apoptosis in SKN cells unlike curcumin that also has a pro-apoptotic potential in SKN cells.

Research Highlights
► AKT-mTOR pathway constitutive activation sustains human uterine LMS cell growth.
► Curcumin inhibits mTOR activity and disrupts the growth of human uterine LMS cells.
► Curcumin induces apoptosis in human uterine LMS cells

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gynecologic Oncology - Volume 122, Issue 1, July 2011, Pages 141–148
نویسندگان
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