HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

Al-Haidari, Amr; Syk, Ingvar; Thorlacius, Henrik

doi:10.1016/j.bbrc.2014.02.078

Cited by 28 publications

(28 citation statements)

References 29 publications

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“…Moreover, mevastatin is thought to enhance the anti-proliferative effects of butyrate (a dietary short-chain fatty acid) in Caco2 colorectal cancer cells through inducing a cell cycle arrest (Wachtershauser, 2001). In addition to this, colorectal cancer cell invasion and metastasis are also thought to be targeted by statins (Kusama et al , 2003; Al-Haidari et al , 2014). Importantly in the context of this review, simvastatin has been shown to enhance the effect of radiation in-vitro on colorectal cancer cells by upregulating apoptosis in these cells (Lim et al , 2015).…”

Section: Discussionmentioning

confidence: 99%

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

et al. 2017

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Background:Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20–30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised.Methods:A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis.Results:The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients.Conclusions:Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.

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Section: Discussionmentioning

confidence: 99%

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

et al. 2017

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“…This indicates the potential for using GGTase-I inhibitors in CRC therapy. A point worth noting is that stains like simvastatin are capable of inhibiting the proliferation and migration of colon cancer cells (14,15), while geranylgeraniol, which can be taken up by cells and converted to geranylgeranyl diphosphate, may reverse the anti-tumor effects of stains (15). These findings suggest that the effects of stains on colon cancer cells might be mediated by interfering with geranylgeranylation of certain proteins.…”

Section: Qualitative Detection Of C35 Mrna Expressionmentioning

confidence: 98%

C35 is overexpressed in colorectal cancer and is associated tumor invasion and metastasis

Dong

Huang

Kong

et al. 2015

BST

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“…Other authors have shown that SIM is a powerful suppressor of the human colon cancer cell migration dependent on chemokine (C-C motif) (CCL-17) via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, thus indicating a possible benefit in antagonizing colon cancer cell metastasis (Al-Haidari et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Optimizing long-circulating liposomes for delivery of simvastatin to C26 colon carcinoma cells

Porfire

Tomuță

Muntean

et al. 2014

Journal of Liposome Research

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Simvastatin (SIM) is a lipophilic statin that has potential benefits for prevention and treatment of several types of malignancies. However, its low water solubility and the toxicity associated with administration of high doses recommend it for encapsulation in carriers able to deliver the therapeutic dose in the tumor. In this work, liposomes with long-circulating properties were proposed as delivery systems for SIM. The objective of this study was to optimize the formulation of SIM-loaded long-circulating liposomes (LCL-SIM) by using D-optimal experimental design. The influence of phospholipids concentration, phospholipids to cholesterol molar ratio and SIM concentration was studied on SIM liposomal concentration, encapsulation efficiency and liposomal size. The optimized formulation had liposomal SIM concentration 6238 µg/ml, EE % of 83.4% and vesicle size of 190.5 nm. Additionally we evaluated the in vitro cytotoxicity of the optimized liposomal SIM (LCL-SIM-OPT) on C26 murine colon carcinoma cells cultivated in monoculture as well as in co-culture with murine peritoneal macrophages at a cell density ratio that provides an approximation of physiological conditions of colon carcinoma development in vivo. Our preliminary studies suggested that LCL-SIM-OPT exerted cytotoxicity on C26 cells probably via enhancement of oxidative stress in co-culture environment.

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HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

Cited by 28 publications

References 29 publications

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

C35 is overexpressed in colorectal cancer and is associated tumor invasion and metastasis

Optimizing long-circulating liposomes for delivery of simvastatin to C26 colon carcinoma cells

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