Curcumin targets the AKT–mTOR pathway for uterine leiomyosarcoma tumor growth suppression

Wong, Tze Fang; Takeda, Takashi; Li, Bin; Tsuiji, Kenji; Kondo, Akiko; Tadakawa, Mari; Nagase, Satoru; Yaegashi, Nobuo

doi:10.1007/s10147-013-0563-4

Cited by 23 publications

(20 citation statements)

References 29 publications

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“…Curcumin has been demonstrated to possess an antitumor effect in numerous types of cancer (9)(10)(11). Treatment with either letrozole or curcumin inhibited the xenografted endometrial tumor growth by inducing apoptosis in tumor cells, and the combination of letrozole and curcumin further strengthened the inhibitory effect on tumor growth (12).…”

Section: Discussionmentioning

confidence: 99%

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

et al. 2015

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Abstract. Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signalregulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC.

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Section: Discussionmentioning

confidence: 99%

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

et al. 2015

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“…Curcumin, derived from the herb Curcuma longa, inhibits uterine LMS cell proliferation both in vitro and in vivo experimental models through AKT-mTOR pathway [105,106], and the m-TOR inhibitor everolimus decelerates LMS growth in mice and prolongs their lifespan [107]. Temserolimus obtained PR in three of six patients with advanced LMS refractory to standard chemotherapy [108].…”

Section: Mammalian Target Of Rapamycin Inhibitorsmentioning

confidence: 99%

Pharmacological treatment for uterine leiomyosarcomas

Gadducci

Guerrieri

2014

Expert Opinion on Pharmacotherapy

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DOX alone, gemcitabine alone, DOX + dacarbazine and gemcitabine + docetaxel may be treatment options for first-line and second-line therapies. However, the clinical benefit of the combination chemotherapy versus single-agent chemotherapy is still debated. Trabectedin is a promising agent for recurrent uterine LMS, able to obtain a prolonged disease control, with 3-month and 6-month progression-free survival rates exceeding 50 and 30%, respectively, and with sometimes unexpectedly durable responses. Pazopanib is the only approved targeted therapy. Hormone therapy with aromatase inhibitors may be a therapeutic option in heavily treated patients with slowly progressive, steroid receptor-positive tumors. Whenever possible, women with recurrent uterine LMS should be encouraged to enter well-designed clinical trials aimed to detect novel active agents.

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“…Preclinical studies have identified additional pathways as potential targets in the treatment of leiomyosarcoma [64-67]. A subset of uLMS shows a loss of PTEN, resulting in aberrant signaling and increased activation of the AKT-mTOR pathway, which leads to unregulated cell proliferation.…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

“…Similar to rapamycin, data from preclinical studies demonstrated that curcumin also targets the AKT-mTOR pathway and can decrease mTOR phosphorylation, as well as downstream targets, including S6 ribosomal proteins. Unlike rapamycin, curcumin also has the ability to induce apoptosis, suggesting that it may be more potent than rapamycin [66, 67]. Other authors have demonstrated the ability of curcumin to also increase autophagy and activate the ERK1/2 pathway.…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

The role of adjuvant therapy in uterine leiomyosarcoma

Ducie

Leitao

2015

Expert Review of Anticancer Therapy

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Summary Uterine leiomyosarcoma (uLMS) is a rare mesenchymal tumor of the gynecologic tract. Although diagnosed in only 1-3% of patients with uterine cancer, uLMS accounts for the majority of uterine cancer-related deaths. The standard of care for patients with uLMS includes total hysterectomy and bilateral salpingo-oophorectomy (BSO). There are no standard recommendations regarding adjuvant or palliative therapy. Many cytotoxic and targeted agents have been studied in clinical trials in an effort to identify an effective therapy that may alter the natural history of this disease. Unfortunately, as of now, there are no adjuvant therapy regimens that improve overall survival in this patient population. There is, therefore, an unmet need to identify a novel therapy that will improve the survival of women diagnosed with this aggressive disease. The current review aims to summarize the existing literature on adjuvant therapy in uLMS, specifically highlighting advances made in the last 5 years.

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Curcumin targets the AKT–mTOR pathway for uterine leiomyosarcoma tumor growth suppression

Abstract: Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT-mTOR pathway for inhibition.

Cited by 23 publications

References 29 publications

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

Pharmacological treatment for uterine leiomyosarcomas

The role of adjuvant therapy in uterine leiomyosarcoma

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