Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Jiang, Weiqin; Fu, Fangfang; Li, Yang-xia; Wang, Weibin; Wang, Haohao; Jiang, Haiping

doi:10.1631/jzus.b1100340

Cited by 22 publications

(24 citation statements)

References 84 publications

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“…All experiments were performed according to the regulations of the Animal Care Committee of Jilin university. To generate CRSC xenografts, 1x10 5 CRSCs were resuspended in PBS (100 µl) and injected subcutaneously into the right flank of the mice. The weight and size of the tumors were measured every other day.…”

Section: Crsc Xenograft Studies Severe Combined Immunodeficiency (Scmentioning

confidence: 99%

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Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells

Zhang

Tian

Song³

et al. 2015

Oncology Reports

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Abstract. Salinomycin is a monocarboxylic polyether antibiotic that has been reported to induce apoptosis in various types of cancer cells with specificity for cancer stem cells. However, its anticancer effect in colorectal cancer stem cells has never been reported. In the present study, we examined the ability of salinomycin to induce cell death in the colorectal cancer stem cell line CD44 + EpCAM + HCT-116, and we measured its in vivo tumor inhibition capacity. Salinomycin dose-dependently induced cytotoxicity in the CD44 + EpCAM + HCT-116 cells and inhibited colony formation. Salinomycin treatment was shown to induce apoptosis, as evidenced by nuclear fragmentation, an increase in the proportion of acridine orange/ethidium bromide-positive cells and an increase in the percentage of Annexin V-positive cells. Apoptosis was induced in colorectal cancer stem cells in a caspase-dependent manner, as shown by an increase in the levels of cleaved caspase-3, -8 and -9. JC-1 staining further revealed that salinomycin induced colorectal cancer cell apoptosis via the mitochondrial pathway. In addition, salinomycin treatment of xenograft mice inhibited the growth of tumors derived from the CD44 + EpCAM + HCT-116 cells. The present study demonstrated that the antibiotic salinomycin exerts an anti-colorectal cancer effect in vitro and in vivo, suggesting salinomycin as a potential drug for colorectal cancer therapy. IntroductionColorectal cancer (CRC) is the third most common malignancy worldwide, accounting for ~10% of all cancer cases and CRC is one of the most common causes of death related to gastrointestinal cancers (1-3). Although the incidence rates of colon cancer have declined somewhat, current therapies are associated with serious side-effects, high cost and recurrence rates exceeding 50%, primarily due to the development of acquired chemoresistance to conventional chemotherapeutics (4,5).Emerging data suggest that malignant tumors contain a small distinct population of cancer stem cells (CSCs), which are responsible for tumor initiation and propagation (6). Stem cell research and the cancer stem cell (CSC) hypothesis have shown that colonic stem cells or CSCs are involved in tissue regeneration and colonic carcinogenesis (7-9). Drug-resistant CSCs are thought to be one of the key causes of CRC treatment failure, and it is hypothesized that these cells are ultimately the likely cause of metastasis and tumor recurrence (10-12). Most modern treatments are ineffective against solid tumors and this may be the result of the increased resistance of CSCs (13). Therefore, it is vital to find novel therapeutic methods to eradicate CSCs and enable the development of more effective treatment protocols (14).Salinomycin is a 751-Da monocarboxylic polyether antibiotic, which was initially used to eliminate bacteria, fungi and parasites and is fed to ruminants to improve nutrient absorption and feeding efficiency (15,16). This compound is now considered an important anticancer drug candidate (17,18). It has recently been reporte...

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Section: Crsc Xenograft Studies Severe Combined Immunodeficiency (Scmentioning

confidence: 99%

“…Although the incidence rates of colon cancer have declined somewhat, current therapies are associated with serious side-effects, high cost and recurrence rates exceeding 50%, primarily due to the development of acquired chemoresistance to conventional chemotherapeutics (4,5).…”

Section: Introductionmentioning

confidence: 99%

Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells

Zhang

Tian

Song³

et al. 2015

Oncology Reports

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“…Patients who have been diagnosed with early stage CRC frequently are treated with surgery in conjunction with chemotherapy and radiotherapy to improve their survival rate (1). However, for the majority of patients diagnosed with CRC have already reached an advanced pathological stage, chemotherapy is the major form of treatment (5)(6)(7)(8). In particular, 5-fluorouracil (5-FU)-based regimens are used as the international standard for late-stage CRC treatment (9,10).…”

Section: Introductionmentioning

confidence: 99%

Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways

et al. 2017

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Abstract. The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks. At present, anti-tumor agents are often single-targeted and therefore are not always therapeutically effective. Moreover, long-term use of these anti-tumor agents often generates drug resistance and potential side effects. These problems highlight the urgent need for the development of novel and more effective anti-cancer drugs. Hedyotis diffusa Willd (HDW) has been used as a major component in traditional Chinese medicine for the clinical treatment of colorectal cancer, with a limited number of adverse effects. However, the molecular mechanisms, which underlie its anti-cancer activity, still require further elucidation. In the present study, using xenograft models and various different human CRC cell lines, the efficacy of the ethanol extract of HDW (EEHDW) against tumor growth was evaluated, and its underlying molecular mechanisms of action were investigated. It was demonstrated that EEHDW was able to inhibit cancer growth in vivo and in vitro. Furthermore, EEHDW was able to suppress the activation of several CRC-associated signaling pathways and was able to regulate the expression of various inflammatory and angiogenic factors. This resulted in the induction of apoptosis and inhibition of cellular proliferation, as well as tumor angiogenesis. The present study demonstrated that EEHDW is able to exhibit anti-cancer activity due to its ability to affect multiple intracellular targets, which suggests that it may be a novel multi-potent therapeutic agent for the treatment of colorectal cancer.

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“…İrinotecan is a topoisomerase I inhibitor; and oxaliplatin is a platinum-based compound and bulky DNA adduct (Wolpin and Mater, 2008). Standard treatment has evolved from 5-FU, with a median overall survival of 10-12 months and an overall response rate of 10%, to combinations of oxaliplatin and irinotecan that have dramatically improved survival to 14-16 months (Best et al, 2000;Jiang et al, 2012). When compared to surgery alone, it is clear that conventional chemotherapies have a relatively modest effect on CRC (Saltz, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…It inhibits angiogenesis by binding to VEGF A, as well as cetuximab and panitumumab, which are monoclonal antibodies that block, EGFR (Van Loon and Venook, 2012). With the introduction of targeted therapy, the overall survival of metastasized CRC patients has been further prolonged (Jiang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Anticancer Effect of COX-2 Inhibitor DuP-697 Alone and in Combination with Tyrosine Kinase Inhibitor (E7080) on Colon Cancer Cell Lines

Altun¹,

Turgut²,

Kaya³

2014

Asian Pacific Journal of Cancer Prevention

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Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Cited by 22 publications

References 84 publications

Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells

Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells

Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways

Anticancer Effect of COX-2 Inhibitor DuP-697 Alone and in Combination with Tyrosine Kinase Inhibitor (E7080) on Colon Cancer Cell Lines

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