Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells

Bartucci, Monica; Svensson, Susanne; Ricci–Vitiani, Lucia; Dattilo, Rosanna; Biffoni, Mauro; Signore, Michele; Ferla, Rita; Maria, Ruggero De; Surmacz, Eva

doi:10.1677/erc-10-0083

Cited by 58 publications

(47 citation statements)

References 61 publications

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“…Stem cells of the gastrointestinal tract may serve as a principal target of tumorigenic mutations due to their naturally long life-span and capacity for self-renewal. The concept of stem cell-driven tumorigenesis in CRC is supported by the identification and phenotypic characterization of a subpopulation of colon cancer cells capable of initiation and sustained reproduction of human colon carcinomas in immune-compromised mice (tumor-initiating cells or colorectal tumor stem cells) (27). Cancer stem cells (CSCs) form spheres when cultured in vitro in serum-free suspension cultures.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, leptin increased the number and size of tumorspheres formed by HCT 116, LS174T and CaCo-2 cells. Bartucci et al reported that leptin enhances the formation of tumorsphere by increasing their size and number (27). Therefore, leptin may affect the growth and survival of CRC stem cells that promote colorectal carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Leptin-induced adhesion and invasion in colorectal cancer cell lines

et al. 2014

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Abstract. Leptin, which is encoded by the obese gene, is a multifunctional neuroendocrine peptide that regulates appetite, bone formation, reproductive function and angiogenesis. The aims of the present study were to investigate the expression of leptin in 80 patients with colorectal cancer (CRC) and to determine the effects of leptin on the malignant properties of CRC cells. We evaluated the expression of leptin in tissues of 80 patients with CRC. Suspension cultures were used to isolate CRC stem cells following pretreatment with leptin. We analyzed the effects of leptin on the adhesion and invasive capacities of CRC cell lines. The effects of leptin on JAK and ERK activation were examined using western blotting. Leptin expression was associated with CRC progression and increased the number and size of spheroid formation by CRC cell lines. Leptin enhanced cell invasion and adhesion and activated JAK and ERK signaling in the CRC cell lines. The present study demonstrated that leptin influences the growth and survival of CRC stem cells and regulates adhesion and invasion of colorectal carcinoma through activation of the JAK and ERK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Leptin-induced adhesion and invasion in colorectal cancer cell lines

et al. 2014

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“…Uważa się bowiem, że obserwowane zwiększenie liczby zachorowań na raka jelita grubego w krajach rozwiniętych może być wynikiem siedzącego trybu życia i zbyt dużej podaży kalorii [37]. Również liczba zgonów z powodu tej choroby w pewnym stopniu zależy od wskaźnika masy ciała (body mass index -BMI) [38].…”

Section: Aktywność Fizycznaunclassified

What is new in gastrointestinal cancer prevention - a review of the literature 2009-2010

Klusek¹,

Głuszek²,

Kozieł³

2011

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“…Similarly, leptin has been shown to increase colon cancer resistance to 5-FU treatment via activation of the PI3K/Akt pathway. 41 Mueller et al studied the effect of BEZ235 and irinotecan on HT-29 cells and showed that BEZ235 increased the effect of irinotecan. 42 This study indicates that inhibition of the PI3K/Akt/mTOR pathway can be combined with a …”

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confidence: 99%

Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis

Zou¹,

Li²,

Carcedo³

et al. 2016

IJN

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Colon cancer is the third most common cancer in the world, with drug resistance and metastasis being the major challenges to effective treatments. To overcome this, combination therapy with different chemotherapeutics is a common practice. In this study, we demonstrated that paclitaxel (PTX) together with BEZ235 exhibited a synergetic inhibition effect on colon cancer cell growth. Furthermore, nanoemulsion (NE)-loaded PTX and BEZ235 were more effective than the free drug, and a combination treatment of both NE drugs increased the efficiency of the treatments. BEZ235 pretreatment before adding PTX sensitized the cancer cells further, suggesting a synergistic inhibition effect through the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin pathway. The 50% inhibitory concentrations for BEZ235 were 127.1 nM and 145.0 nM and for PTX 9.7 nM and 9.5 nM for HCT-116 and HT-29 cells, respectively. When loaded with NE the 50% inhibitory concentrations for BEZ235 decreased to 52.6 nM and 55.6 nM and for PTX to 1.9 nM and 2.3 nM for HCT-116 and HT-29 cells, respectively. Combination treatment with 10 nM NE-BEZ235 and 0.6 nM and 1.78 nM NE-PTX could kill 50% of HCT-116 and HT-29, respectively. The cell death caused by the treatment was through apoptotic cell death, which coincided with decreased expression of anti-apoptotic protein B-cell lymphoma 2. Our data indicate that the combination therapy of PTX with the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin dual inhibitor BEZ235 using NE delivery may hold promise for a more effective approach for colon cancer treatment.

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Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells

Cited by 58 publications

References 61 publications

Leptin-induced adhesion and invasion in colorectal cancer cell lines

Leptin-induced adhesion and invasion in colorectal cancer cell lines

What is new in gastrointestinal cancer prevention - a review of the literature 2009-2010

Synergistic inhibition of colon cancer cell growth with nanoemulsion-loaded paclitaxel and PI3K/mTOR dual inhibitor BEZ235 through apoptosis

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