Recent Progress in Mass Spectrometry-based Metabolomics for Colorectal Cancer

Metabolomics, one of the latest omics technologies, is employed to reveal overall metabolic trajectories, identify disease causative mechanisms and provide information for preventive diagnosis and drug targeting. Cancer is a disease known to alter cellular metabolism and so metabolomics can play an important role in the early diagnosis of cancer and in the evaluation of medical interventions and treatments for cancer. Many metabolomics studies rely on high-sensitive and high-throughput mass spectrometry platforms. In recent years, various mass spectrometry(MS) methodologies have been developed and enriched the scope of metabolite detection, contributing to disease studies, such as diabetes, cancer, and depression. Colorectal cancer is the third most diagnosed cancer worldwide and its incidence ranked third in China. This review focuses on the mass spectrometry technologies in metabolomics and summarizes the progress of metabolomics research in colorectal cancer.     

Allicin inhibits mouse colorectal tumorigenesis through suppressing the activation of STAT3 signaling pathway

Allicin is the major biologically active compounds of freshly crushed garlic. It has been reported to inhibit the proliferation and promote the apoptosis of multiple colorectal cancer cells. However, the anti-colorectal cancer effect of Allicin has not been verified by in vivo studies. In the present study, we investigated the effect of Allicin on azoxymethane/dextran sodium sulfate (AOM/DSS) colorectal cancer mouse model and explore the underlying possible mechanism. Our result showed that Allicin could inhibit colonic tumorigenesis of AOM/DSS mice in vivo. In vitro study showed that Allicin promoted the apoptosis and suppressed the survival and proliferation of HCT116 cells. The molecular mechanism is related to the suppression of STAT3 signaling activation. Thus, our data provide further support for Allicin as a potential favorable supplement for human colorectal cancer.     

Involvement of mitophagy-mediated cell death in colon cancer cells by folate-appended methyl-β-cyclodextrin

In recent years, colorectal cancer has gained great attention among various types of cancers. We previously synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) as a novel autophagic antitumor agent. In this study, to further elucidate the impact of FA-M-β-CyD as an antitumor agent, we evaluated cytotoxic activity and the antiproliferative effect in colon cancer cells and colorectal cancer model mice, respectively. As a result, FA-M-β-CyD showed potent cytotoxic activity in HCT116 cells, a human colon cancer cell line, through folate receptor-α (FR-α)-mediated cellular uptake. In addition, FA-M-β-CyD elicited autophagosome formation and induced mitophagy in HCT116 cells. Importantly, FA-M-β-CyD drastically reduced the number of tumor polyps in colorectal cancer model mice induced by azoxymethane/dextran sodium sulfate after intravenous injections once a week for 4 weeks. These results suggest that FA-M-β-CyD has the antiproliferative effect in the colorectal cancer, due to the FR-α-mediated endocytosis and mitophagy induction.     

Early Diagnosis of Colorectal Cancer in Rats With DMH Induced Carcinogenesis by Means of Urine Autofluorescence Analysis

Cancer is one of the most highlighted topics of current research. Early detection of this disease allows more effective therapy, hence higher chance of cure. Application of fluorescence spectral techniques into oncological diagnostic is one of the potential alternatives. Chemically induced carcinogenesis in rats is widely used model for exploration of various aspects of colorectal cancer. This study shows value of discriminate analysis of urine fluorescent fingerprint between healthy control group of rats and those with dimethylhydrazine induced early lesions of colorectal cancer. Using fluorescence spectroscopy, significant difference (P < 0.05) between both of group was achieved.     

Cytotoxic activity and cell cycle analysis of hexahydrocurcumin on SW 480 human colorectal cancer cells

The cytotoxicity of hexahydrocurcumin and its effect on the cell cycle in human colorectal cancer cells SW480 has been studied for the first time. The compound, extracted from Zingiber officinale, was shown to be cytotoxic to colorectal cancer cells. Treatment of SW480 cells with hexahydrocurcumin (100 microM) resulted in a massive accumulation of the cells in the G1/G0 phase of the cell cycle. The cytotoxic effect of hexahydrocurcumin may prove useful in cancer prevention.     

Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer

Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research is to investigate the anti-cancer activities of BA purified from Piper retrofractum and study its effect on the expression of HSPA in colorectal cancer HCT116 and SW480 cells. The viability of both cancer cells was reduced after they were treated with an increasing dosage of BA. Flow cytometry assay revealed that levels of cell apoptosis significantly increased after incubation with BA in both cancer cells. Pro-apoptotic markers including Bax, cleaved-caspase-3 and cleaved-caspase-9 were increased while anti-apoptotic marker Bcl-2 was decreased after BA treatment. Western blot also showed that the expression of HSPA fluctuated upon BA treatment, whereby HSPA was increased at lower BA concentrations while at higher BA concentrations HSPA expression was decreased. Preliminary molecular docking assay showed that BA can bind to the nucleotide binding domain of the HSP70 at its ADP-bound state of the HSP70. Although further research is needed to comprehend the BA-HSPA interaction, our findings indicate that BA can be considered as potential candidate for the development of new treatment for colorectal cancer.     

Assessment of the Efficacy of Olive Leaf (Olea europaea L.) Extracts in the Treatment of Colorectal Cancer and Prostate Cancer Using In Vitro Cell Models

Cancer is one of the most serious public health issues worldwide, ranking second only to cardiovascular diseases as a cause of death. Numerous plant extracts have extraordinary health benefits and have been used for centuries to treat a variety of ailments with few side effects. Olive leaves have a long history of medicinal and therapeutic use. In this study, the anti-cancer properties of an olive leaf extract were investigated in vitro using colorectal and prostate cancer cell lines (HT29 and PC3, respectively). A high-performance liquid chromatography analysis showed that the olive leaf extract contained a high chlorogenic acid content. Accordingly, chlorogenic acid may be related to the observed effects of the aqueous extract on cancer cells, including increased inhibition of cancer cell growth, migration, DNA fragmentation, cell cycle arrest at the S phase, reactive oxygen species (ROS) production, and altered gene expression. The effects of the extracts were greater in HT29 than in PC3 cells. These results suggest that chlorogenic acid, the main constituent in the olive extract, is a promising new anti-cancer agent. Further analyses should focus on its in vivo effects on colorectal tumor models, both alone and in combination with established agents.     

Identification of Colorectal Cancer Using Near-Infrared Spectroscopy and Adaboost with Decision Stump

Rapid and objective detection of cancer is crucial for successful treatment. Near-infrared (NIR) spectroscopy is a vibrational technique capable of optically probing molecular changes associated with disease. The purpose of this study was to explore NIR spectroscopy for discriminating cancer from normal colorectal tissues. A total of 110 tissue samples from patients who underwent operations were characterized in this study. The popular ensemble technique AdaBoost was used to construct the diagnostic model. A decision stump was used as the weak learning algorithm. Adaboost with decision stump, an ensemble of weak classifiers, was compared with the most suitable single model, a strong classifier. Only the 20 most significant variables were selected as inputs for the model based on measured defined variable importance. Using an independent test set, the single strong classifier provided diagnostic accuracy of 89.1%, sensitivity of 100%, and specificity of 78.6%, whereas the ensemble of weak stumps provided accuracy of 96.3%, sensitivity of 96.3%, and specificity of 96.3% for distinguishing cancer from normal colorectal tissues. Therefore, NIR spectroscopy in combination with AdaBoost with decision stumps has demonstrated potential for rapid and objective diagnosis of colorectal cancer.     

Anticancer Activity of 2-O-caffeoyl Alphitolic Acid Extracted from the Lichen,Usnea barbata 2017-KL-10

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens’ metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer.     

核酸适配体在癌症诊断中的研究进展

核酸适配体是通过指数富集配体系统进化技术(SELEX)从体外合成的寡核苷酸文库中筛选得到的短的寡核苷酸分子(ssDNA或RNA).核酸适配体能够通过折叠成特定的空间结构与靶标分子进行特异性结合,与抗体相比,适配体具有高亲和力、易修饰、低成本、易于合成和低免疫原性等优势,可以针对细胞、蛋白质、组织、生长因子进行癌症生物标...     

SKIN CANCER AND ULTRAVIOLET RADIATION

Abstract. A new model is presented for the calculation of the increased incidence of non-melanoma skin cancer in Caucasians resulting from ozone reduction. The model postulates that the probability of first incidence of such skin cancer is distributed log-normally as a function of total accumulated lifetime dose of harmful ultraviolet radiation. The effect on skin cancer incidence of an increase in harmful ultraviolet radiation due to ozone reduction can then be calculated directly from the extent to which each individual's lifetime accumulated dose is thereby increased. The result of such a perturbation, on average, would be to cause skin cancer to appear at a slightly earlier age. Since skin cancer is predominantly a disease of the elderly, this shift to younger ages has the effect, when integrated over the entire population, of increasing the overall total incidence of skin cancer.     

Current Status,Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review

In 2020, an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths have occurred worldwide, with colorectal cancer ranking as the third most frequently diagnosed (10.0%). Several attempts have been conducted against cancer, including surgery, radiation, monoclonal antibodies, and chemotherapy. Many people choose natural products as alternatives against cancer. These products will not only help in human life preservation but also work as a source of up-to-date information, leading people away from incorrect information. We discuss the current status, distribution, and future implications of protecting populations with natural products as an alternative against colorectal cancer in Indonesia. Thirty-eight studies were included in this review for data extraction. The distribution of natural products in Indonesia that have potential activity against colorectal cancer cells was predominated by terpenoids, followed by phytosterols, phenolics, alkaloids, and polyisoprenoids. The type of cell line utilized in the cytotoxic activity analysis of natural products was the WiDr cell line, followed by HT-29 cells and HCT-116 cells. This review showed that MTT in vitro assay is a general method used to analyze the cytotoxic activity of a natural product against colorectal cancer cells, followed by other in vitro and in vivo methods. The systematic review provided predictions for several secondary metabolites to be utilized as an alternative treatment against colorectal cancer in Indonesia. It also might be a candidate for a future co-chemotherapy agent in safety, quality, and standardization. In addition, computational methods are being developed to predict the drug-likeness of compounds, thus, drug discovery is already on the road towards electronic research and development.     

Single nucleotide polymorphism detection in the hMSH2 gene using conformation-sensitive CE

CE allows for highly reproducible analysis of DNA fragments which can be used to detect DNA mutations including SNPs. We have utilized a simple and direct CE analysis method for SNP analysis called conformation-sensitive CE (CSCE), based on the principle of single nucleotide different to produce conformational changes in the mildly denaturing solvent system. This method was applied to analysis of a mutation in the promoter region of the hMSH2 gene. This gene belongs to the human DNA mismatch repair system, which is responsible for recognizing and repairing mispaired nucleotides, and mutations in the hMSH2 gene are known to cause hereditary nonpolyposis colorectal cancer (HNPCC). PCR fragments generated from the promoter region of the hMSH2 gene, displaying either a C/C homozygote, C/T heterozygote, or T/T homozygote genotype, did not require further pretreatment before electrokinetic injection. The CE separation, using a 1xTris-borate-EDTA (TBE) buffer containing 3% w/v hydroxylethyl cellulose (HEC) and 6 M urea, was performed under reverse polarity with a separation temperature of 15 degrees C. The genotypes of 204 healthy volunteers and 13 colorectal cancer patients were determined using CSCE, and the results confirmed by DNA sequencing. While the CSCE separations were shown to be highly reproducible and sensitive for screening large populations, no correlation was observed between cancer patients and this hMSH2 gene polymorphism.     

Comprehensive fluorogenic derivatization–liquid chromatography/tandem mass spectrometry proteomic analysis of colorectal cancer cell to identify biomarker candidate

Existing colorectal cancer biomarkers are insufficient for providing a quick and accurate diagnosis, which is critical for a good prognosis. More appropriate biomarkers are thus needed. To identify new colorectal cancer biomarker candidates, we conducted a comprehensive differential proteomic analysis of six cancer cell lines and a normal cell line, utilizing a fluorogenic derivatization–liquid chromatography–tandem mass spectrometry (FD‐LC‐MS/MS) approach. Two sets of intracellular biomarker candidates were identified: one for colorectal cancer, and the other for metastatic colorectal cancer. Our results suggest that cooperative expression of FABP5 and cyclophilin A might be linked to Her2 signaling. Upregulation of LDHB and downregulation of GAPDH suggest the existence of a specific nonglycolytic energy production pathway in metastatic colorectal cancer cells. Downregulation of 14‐3‐3ζ/δ, cystatin‐B, Ran and thioredoxin could be a result of their secretion, which then stimulates metastasis via activity in the sera and ascitic fluids. We propose a possible flow scheme to describe the dynamics of protein expression in colorectal cancer cells leading to tumor progression and metastasis via cell proliferation, angiogenesis, disorganization of actin filaments and epithelial–mesenchymal transition. Our results suggest that colorectal tumor progression may be regulated by signaling mediated by Her2, hypoxia, and TGFβ. Copyright © 2012 John Wiley & Sons, Ltd.     

水溶性CdTe量子点荧光探针检测肠癌相关T抗原

直接合成性能优良的水溶性CdTe量子点,然后在其表面成功修饰花生凝集素,经过凝胶柱的分离纯化获得功能化的量子点荧光探针.基于T抗原选择性与花生凝集素(PNA)结合的特性,利用该探针对肠癌中高表达的T抗原进行检测,且与传统的荧光染料标记的免疫荧光分析进行了比较.实验结果表明:该功能化的荧光探针能够有效地识别肠癌的相关T抗原,从而为T抗原的检测以及肠癌的临床诊断与愈后判断提供了一种新的方法.     

Gamma-mangostin, a micronutrient of mangosteen fruit, induces apoptosis in human colon cancer cells

Recently colorectal cancer rates have increased rapidly in Taiwan. The treatment of colorectal cancer includes surgery, radiation therapy and chemotherapy. Mangosteen (Garcinia mangostana) is a famous Asian tropical fruit. γ-Mangostin is a xanthone derivative isolated from the fruit hull. In previous studies, we found evidence of anti-inflammatory and anti-brain tumor activities in γ-mangostin. In this study, we performed further studies to assess the apoptotic effects of γ-mangostin on colorectal adenocarcinoma cells HT29. γ-Mangostin showed concentration and time-dependent cytotoxic effects on HT29 cells. Microscopic observation under Giemsa staining showed that γ-mangostin induced cellular swelling and the appearance of apoptotic bodies, characteristic of apoptosis in HT29 cells. In addition, flow cytometry analysis showed an increase of hypodiploid cells in γ-mangostin-treated HT29 cells, while enhancement of intracellular peroxide production was detected in the same γ-mangostin-treated cells by DCHDA assay and DiOC6(3) staining. In view of the above results, γ-mangostin has demonstrated anticancer activity and induces apoptosis in HT29 colorectal adenocarcinoma cells. The evidence suggests that γ-mangostin could serve as a micronutrient for colon cancer prevention and is a potential lead compound for the development of anti-colon cancer agents.     

Chemical-Genetic Interactions of Bacopa monnieri Constituents in Cells Deficient for the DNA Repair Endonuclease RAD1 Appear Linked to Vacuolar Disruption

Colorectal cancer is a common cancer worldwide and reduced expression of the DNA repair endonuclease XPF (xeroderma pigmentosum complementation group F) is associated with colorectal cancer. Bacopa monnieri extracts were previously found to exhibit chemical-genetic synthetic lethal effects in a Saccharomyces cerevisiae model of colorectal cancer lacking Rad1p, a structural and functional homologue of human XPF. However, the mechanisms for B. monnieri extracts to limit proliferation and promote an apoptosis-like event in RAD1 deleted yeast was not elucidated. Our current analysis has revealed that B. monnieri extracts have the capacity to promote mutations in rad1∆ cells. In addition, the effects of B. monnieri extracts on rad1∆ yeast is linked to disruption of the vacuole, similar to the mammalian lysosome. The absence of RAD1 in yeast sensitizes cells to the effects of vacuole disruption and the release of proteases. The combined effect of increased DNA mutations and release of vacuolar contents appears to induce an apoptosis-like event that is dependent on the meta-caspase Yca1p. The toxicity of B. monnieri extracts is linked to sterol content, suggesting saponins may be involved in limiting the proliferation of yeast cells. Analysis of major constituents from B. monnieri identified a chemical-genetic interaction between bacopasaponin C and rad1∆ yeast. Bacopasaponin C may have potential as a drug candidate or serve as a model for the development of analogs for the treatment of colorectal cancer.     

增强CT联合血清指标诊断结直肠癌的价值

本文探讨癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及增强CT在结直肠癌中的联合诊断效果。选取100例结直肠癌患作为观察组,同时选取结直肠良性肿瘤患者60例作为对照组,检测血清CEA、CA19-9、IGFBP-3,同时给予增强CT检查。观察组血清CEA和CA19-9高于对照组(P<0.05),而IGFBP-3低于对照组(P<0.05);TNM分期Ⅲ~Ⅳ和Ⅰ~Ⅱ患者血清CEA、CA19-9和IGFBP-3差异比较有统计学意义(P<0.05);增强CT联合血清指标联合诊断灵敏性为89.00%、特异性为90.00%;增强CT诊断结直肠癌T分期、N分期与病理结果Kappa值分别为0.696和0.790(P<0.05)。CEA、CA19-9、IGFBP-3联合增强CT是一种具有较高效能的结直肠癌诊断方法。