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Published on: June 18, 2015
Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition
Tze Fang Wong1, Takashi Takeda, Bin Li
1Department of Obstetrics and Gynecology, Sendai, Japan.
Objective:
Uterine 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.
Methods:
Human 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.
Results:
Both 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.
Conclusions:
Curcumin 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.
Insights
Curcumin effectively inhibits uterine leiomyosarcoma cell growth by targeting the AKT-mTOR pathway. Unlike rapamycin, curcumin also demonstrates a significant pro-apoptotic effect in these cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Uterine leiomyosarcoma exhibits poor response to conventional chemotherapy.
- Loss of PTEN leads to AKT-mTOR pathway activation, promoting leiomyosarcoma.
- Curcumin, from Curcuma longa, possesses known antitumor properties.
Purpose of the Study:
- To investigate the antitumor effects of curcumin on uterine leiomyosarcoma cells.
- To explore curcumin as a potential alternative to standard chemotherapy.
- To elucidate the mechanism of curcumin's action on leiomyosarcoma.
Main Methods:
- In vitro culture of human leiomyosarcoma cell lines (SKN, SK-UT-1).
- Treatment with varying doses of rapamycin or curcumin.
- Assessment of cell proliferation (MTS assay), protein phosphorylation (Western Blotting), and apoptosis (Western Blotting, Caspase-3 assay, TUNEL assay).
Main Results:
- Both rapamycin and curcumin reduced SKN cell proliferation.
- Curcumin inhibited mTOR, p70S6, and S6 phosphorylation, similar to rapamycin.
- Curcumin significantly induced apoptosis in SKN cells in a dose-dependent manner, while rapamycin did not.
Conclusions:
- Curcumin inhibits uterine leiomyosarcoma cell growth by targeting the AKT-mTOR pathway.
- Curcumin exhibits a pro-apoptotic effect on uterine leiomyosarcoma cells, distinct from rapamycin's effects.
- Curcumin represents a promising therapeutic agent for uterine leiomyosarcoma.
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