Hyperthermia and protein homeostasis: Cytoprotection and cell death.

Protein homeostasis or proteostasis, the correct balance between production and degradation of proteins, is an essential pillar for proper cellular function. Among the several cellular mechanisms that disrupt homeostatic conditions in cancer cells, hyperthermia (HT) has shown promising anti-tumor effects. However, cancer cells are also capable of thermoresistance. Indeed, HT-induced protein denaturation and aggregation results in the up regulation of heat shock proteins, a group of molecular chaperones with cytoprotective and anti-apoptotic properties via stress-inducible transcription factor, heat shock factor 1(HSF1). Heat shock proteins assist in the refolding of misfolded proteins and aids in their elimination if they become irreversibly damaged by various stressors. Furthermore, HSF1 also initiates the unfolded protein response in the endoplasmic reticulum (ER) to assist in the protein folding capacity of ER and also promotes the translation of pro-survival proteins' mRNA such as activating transcription factor 4 (ATF 4). Moreover, HT associated induction of microRNAs is also involved in thermal resistance of cancer cells via up-regulation of anti-apoptotic Bcl-2 proteins and down regulation of pro-apoptotic Bax and caspase 3 activities. Another cellular protection in response to stressors is Autophagy, which is regulated by the Mammalian target of rapamycin (mTOR) protein. Kinase activity in mTOR phosphorylates HSF1 and promotes its nuclear translocation for heat shock protein synthesis. Over-expression of heat shock proteins are reported to up-regulate Beclin-1, an autophagy initiator. Moreover, HT-induced reactive oxygen species (ROS) generation is sensitized by transcription factor NF-E2 related factor 2 (Nrf2) and activates the cellular expression of antioxidants and autophagy gene. Furthermore, ROS also potentiates autophagy via activation of Beclin-1. Inhibition of thermotolerance can potentiate HT-induced apoptosis. Here, we outlined that heat stress alters cellular proteins which activates cellular homeostatic processes to promote cell survival and make cancer cells thermotolerant.

In vitro and in vivo anti-Helicobacter pylori activity of selected medicinal plants employed for the management of gastrointestinal disorders.

Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria chamomilla L. and Foeniculum vulgare Mill. were selected for their in vitro and in vivo evaluation of anti-Helicobacter pylori activity. In vitro evaluation was performed by using disk diffusion method and minimum inhibitory concentrations were noted while rat models were selected for in vivo activity against four Helicobacter pylori strains isolated form gastric mucosa. Mentha piperita showed largest zone of inhibition with 9 mm diameter among all other extracts. All the plants showed promising anti-Helicobacter pylori activity against four isolates and a reference strain at concentrations of 125, 250, 500 and 1000 µg/ml in comparison with Amoxicillin 1 µg/ml but least MIC was exhibited by Mentha piperita followed by in vivo testing where it competed Amoxicillin at 1000 mg/kg by achieving 80% eradication of Helicobacter pylori in mucosa of infected rats justified by histological examination of stomach. It was concluded that medicinal plants possess strong anti-Helicobacter pylori activity and can be considered a potential source of safe and effective alternative regimens for the eradication of Helicobacter pylori.

Can Diet Modulate Helicobacter pylori-associated Gastric Pathogenesis? An Evidence-Based Analysis.

Helicobacter pylori is involved in the pathogenesis of gastritis, peptic ulcer, and gastric cancer. The infection is prevalent in more than half of the world's population. Although the infection may lead to detrimental consequences, still the majority of the infected individuals only develop mild gastritis. Several factors are behind this paradoxical outcome including virulence of the infecting H. pylori strains, genetic background of the host, and factors related to lifestyle such as dietary habits. Among these, lifestyle including dietary factors was not in the limelight, until recently, as one of the important factors that could modulate H. pylori-linked gastric diseases. This review is directed to gather and elucidate the role of dietary components in augmenting or attenuating pathological processes initiated by H. pylori. Available evidence strongly supports the notion that the diet may play a critical role in defining the final outcome of H. pylori infection particularly if certain dietary components are taken on a regular basis for a long time. Despite a recent surge in research related to the role of dietary ingredients, further studies involving large-scale clinical trials are required to gain a better understanding of the precise role played by the dietary ingredients in H. pylori-associated pathogenesis.

Enhancement of hyperthermia-induced apoptosis by 5Z-7-oxozeaenol, a TAK1 inhibitor, in Molt-4 cells.

PURPOSE: Transforming growth factor-ß-activated kinase1 (TAK1) plays an anti-apoptotic role in response to multiple stresses. TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) has been studied for its apoptotic effects. However, the combined effect of OZ with physical stresses remains to be elusive. Therefore, in this study we focussed to determine the combined effects of OZ with hyperthermia (HT) using Molt-4 cell line. MATERIALS AND METHODS: Molt-4 cells were pre-treated with OZ for 1 h followed by heat exposure (44 °C, 10 min) and harvested 24 h after incubation at 37 °C, apoptosis was measured by Annexin V-FITC/PI double staining assay using flow cytometry and cell growth was observed by cell counting assay. Further mechanism involved in the combination was investigated by measuring mitochondrial membrane potential (MMP), intracellular ROS generation, expression of apoptosis related protein, intracellular calcium ion level and Fas activity. RESULTS: Combination of OZ with HT significantly enhances MMP loss and superoxide generation. Furthermore, OZ pre-treatment promotes caspase-8 cleavage, Fas externalisation, caspase 3 activity and intracellular calcium ion levels. OZ pre-treatment decreased the expression of HT-induced Bcl-2 and increased the expression of pro-apoptotic Bax, while markedly suppressed the phosphorylation of JNK and p38. In addition, increased expression of CHOP following combined treatment indicates that ER stress may also involve in the enhancement of HT-induced apoptosis. CONCLUSION: Our data showed for the first time that OZ sensitizes Molt-4 cells to HT-induced apoptosis via extrinsic and intrinsic apoptotic pathways. Furthermore, ROS and ER stress may also play role in the enhancement of HT-induced apoptosis by OZ.

Hyperthermia: an effective strategy to induce apoptosis in cancer cells.

Heat has been used as a medicinal and healing modality throughout human history. The combination of hyperthermia (HT) with radiation and anticancer agents has been used clinically and has shown positive results to a certain extent. However, the clinical results of HT treatment alone have been only partially satisfactory. Cell death following HT treatment is a function of both temperature and treatment duration. HT induces cancer cell death through apoptosis; the degree of apoptosis and the apoptotic pathway vary in different cancer cell types. HT-induced reactive oxygen species production are responsible for apoptosis in various cell types. However, the underlying mechanism of signal transduction and the genes related to this process still need to be elucidated. In this review, we summarize the molecular mechanism of apoptosis induced by HT, enhancement of heat-induced apoptosis, and the genetic network involved in HT-induced apoptosis.

Non-cirrhotic Ascites: A Case of Severe Alcoholic Hepatitis.

This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation excluded alternative etiologies, pinpointing sinusoidal non-cirrhotic portal hypertension. Present therapeutic modalities for AH, including steroids and pentoxifylline, offer limited efficacy, necessitating ongoing investigation. Liver transplantation may be contemplated in refractory cases. This case underscores the intricate nature of AH presentations and the challenges in their management, emphasizing the imperative need for continued research to delineate optimal therapeutic strategies. Early intervention remains pivotal in addressing AH complications, underscoring the need for heightened clinical vigilance and proactive treatment approaches in such cases.

Treating cancer with heat: hyperthermia as promising strategy to enhance apoptosis.

The fundamental idea and the effects of heat on cancer cells are well known. However, the results obtained in therapy by hyperthermia (HT) alone have been only partially satisfactory. Treatment at temperatures between .40 and 44 degrees C is cytotoxic for cells in an environment with a low oxygen partial pressure and low pH, conditions that are found specifically within tumour tissue, due to insufficient blood perfusion. Under such conditions radiotherapy is less effective, and systemically applied cytotoxic agents will reach such areas in lower concentrations than in well-perfused areas. Therefore, clinically, it is preferred to use hyperthermia in combination with radiation therapy and chemotherapy. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources; regional hyperthermia by perfusion of organs or limbs, or by irrigation of body cavities; and whole-body hyperthermia. Number of studies have reported the combination of thermo-radiotherapy. Consequently, much attention has been focussed on identifying agents among the conventional chemotherapeutic substances that can sensitise tumour cells to hyperthermia-induced damage with minimal effects on normal cells. In this review, we overviewed important mechanisms of hyperthermia-induced apoptosis and the substances which can act as heat sensitisers in cancer therapy.

Is Greenfield investment improving welfare: A quantitative analysis for Latin American and Caribbean developing countries.

Greenfield investment is considered the backbone of emerging economies and developing countries. This research is carried out to investigate the causal impact of Greenfield investment as a target variable and some other controlled variables for the sample of 23 Latin American and Caribbean (LA&C) developing countries. The period is 1998-2017, and Levin, Lin and Chu (LLC) and System-Generalized Method of Moment (Sys-GMM) techniques are employed for analytical analysis. The Sys-GMM technique estimates show that Greenfield investment has a significant positive impact on these countries' economic growth, health, education, and welfare. Furthermore, controlled variables remittances have a significant and positive impact, while foreign aid has a negative effect on the dependent variables. The rest of the other controlled variables show mixed results. From the analysis, it is suggested that Greenfield investment has improved per capita income, education and health sector that further enhanced the welfare of the society. In addition, new foreign investment creates job employment and brings innovations that improve labour skills. On the other hand, foreign aid must be avoided, which harms the economic activities of developing countries. Therefore, it is concluded that governments of Latin American and Caribbean developing countries adopt more friendly policies to attract Greenfield investment.

Isofraxidin enhances hyperthermia­induced apoptosis via redox modification in acute monocytic leukemia U937 cells.

The cell­killing potential of most chemotherapeutic agents is enhanced by a temperature elevation. Isofraxidin (IF) is a coumarin compound widely found in plants, such as the Umbelliferae or Chloranthaceae families. IF induces anticancer effects in lung and colorectal cancer. To the best of our knowledge, the combined effects of hyperthermia (HT) and IF on heat­induced apoptosis have not been reported. Acute monocytic leukemia U937 cells were exposed to HT with or without IF pre­treatment. Apoptosis was measured by Annexin V­FITC/PI double staining assay using flow cytometry and cell viability was observed by cell counting kit assay, DNA fragmentation. The mechanism involved in the combination was explored by measuring changes in the mitochondrial membrane potential, (MMP), intracellular ROS generation, expression of apoptosis related protein, and intracellular calcium ion level. It was demonstrated that IF enhanced HT­induced apoptosis in U937 cells. The results demonstrated that combined treatment enhanced mitochondrial membrane potential loss and transient superoxide generation increased protein expression levels of caspase­3, caspase­8 and phosphorylated­JNK and intracellular calcium levels. Moreover, the role of caspases and JNK was confirmed using a pan caspase inhibitor (zVAD­FMK) and JNK inhibitor (SP600125) in U937 cells. Collectively, the data demonstrated that IF enhanced HT­induced apoptosis via a reactive oxygen species mediated mitochondria/caspase­dependent pathway in U937 cells.

A novel data balancing approach and a deep fractal network with light gradient boosting approach for theft detection in smart grids.

Electricity theft is the largest type of non-technical losses faced by power utilities around the globe. It not only raises revenue losses to the utilities but also leads to lethal fires and electric shocks at distribution side. In the past, field operation groups were sent by the utilities to conduct inspections of suspicions electric equipments stated by the public. Advanced metering infrastructure based recent development in the smart grids makes it easy to detect electricity thefts. However, the conventional supervised learning techniques have low theft detection performance mainly due to imbalance datasets available for training. Therefore, in this paper, we develop a novel theft detection model with twofold contribution. A unique hybrid sampling technique named as hybrid oversampling and undersampling using both classes (HOUBC) is proposed to balance the dataset. HOUBC first performs undersampling and then oversampling using both the majority (normal) and minority (theft) classes. A new deep learning method, fractal network is applied with light gradient boosting method to extract and learn important characteristics from electricity consumption profiles for identifying electricity thieves. The proposed model relies on smart meter's data for theft detection and hence, a rapid and widespread adaption of this model is feasible, which shows its main advantage. The performance of the model is evaluated with real-world smart meter's data, i.e., state grid corporation of China. Comprehensive simulation results describe the effectiveness of the proposed model against conventional schemes in terms of electricity theft detection.

Chemical inducers of heat shock proteins derived from medicinal plants and cytoprotective genes response.

Environmental stress induces damage that activates an adaptive response in any organism. The cellular stress response is based on the induction of cytoprotective proteins, the so-called stress or heat shock proteins (HSPs). HSPs are known to function as molecular chaperones which are involved in the therapeutic approach of many diseases. Therefore in the current study we searched nontoxic chaperone inducers in chemical compounds isolated from medicinal plants. Screening of 80 compounds for their Hsp70-inducing activity in human lymphoma U937 cells was performed by western blotting. Five compounds showed significant Hsp70 up-regulation among them shikonin was most potent. Shikonin was able to induce Hsp70 at 0.1 µM after 3 h without activation of heat shock transcription factor 1 (HSF-1). It also induces significant reactive oxygen species generation. The expression level of genes responsive to shikonin was studied using global-scale microarrays and computational gene expression analysis tools. Significant increase in the nuclear factor erythroid 2-related factor 2 (Nrf2, NFEL2L2) -mediated oxidative stress response was observed that leads to the activation of HSP. The results of gene chip analysis were further confirmed by real-time qPCR assay. In short, the detailed mechanisms of Hsp70 induction by shikonin is not fully understood, Nrf2 and its target genes might be involved in the Hsp70 up-regulation in U937 cells.

Ins and outs of cadmium-induced carcinogenesis: Mechanism and prevention.

Cadmium (Cd) is a heavy metal and a highly toxic pollutant that is released into the environment as a byproduct of most modern factories and industries. Cd enters our body in significant quantities from contaminated water, cigarette smoke, or food product to many detrimental health hazards. Based on causal association all the Cd-related or derived compounds have been classified as carcinogens. In this study, we present an overview of the published literature to understand the molecular mechanisms for Cd-induced carcinogenesis and its prevention. In acute Cd poisoning production of reactive oxygen species is a key factor. However, chronic Cd exposure can transform cells to become more resistant to oxidative stress. Also, as an epigenetic mechanism Cd acts indirectly on DNA repair mechanisms via alteration of reactions upstream. Those transformed cells acquire resistance to apoptosis and deregulation of calcium homeostasis. Leading to uncontrolled carcinogenic cell proliferation and inherent DNA lesions. Flavonoids commonly found in plant foods have been shown to have a protective effect against Cd-induced carcinogenicity. A wide variety of tumorigenic mechanisms involved in chronic Cd exposure and the beneficial effects of flavonoids against Cd-induced carcinogenicity necessitate further investigations.

What drives general practitioners in the UK to improve the quality of care? A systematic literature review.

BACKGROUND: In the UK, the National Health Service has various incentivisation schemes in place to improve the provision of high-quality care. The Quality Outcomes Framework (QOF) and other Pay for Performance (P4P) schemes are incentive frameworks that focus on meeting predetermined clinical outcomes. However, the ability of these schemes to meet their aims is debated. OBJECTIVES: (1) To explore current incentive schemes available in general practice in the UK, their impact and effectiveness in improving quality of care and (2) To identify other types of incentives discussed in the literature. METHODS: This systematic literature review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six databases were searched: Cochrane, PubMed, National Institute for Health and Care Excellence Evidence, Health Management Information Consortium, Embase and Health Management. Articles were screened according to the selection criteria, evaluated against critical appraisal checklists and categorised into themes. RESULTS: 35 articles were included from an initial search result of 22087. Articles were categorised into the following three overarching themes: financial incentives, non-financial incentives and competition. DISCUSSION: The majority of the literature focused on QOF. Its positive effects included reduced mortality rates, better data recording and improved sociodemographic inequalities. However, limitations involved decreased quality of care in non-incentivised activities, poor patient experiences due to tick-box exercises and increased pressure to meet non-specific targets. Findings surrounding competition were mixed, with limited evidence found on the use of non-financial incentives in primary care. CONCLUSION: Current research looks extensively into financial incentives, however, we propose more research into the effects of intrinsic motivation alongside existing P4P schemes to enhance motivation and improve quality of care.

A Questionnaire-Based Survey to Assess the Level of Knowledge and Awareness about Drug-Food Interactions among General Public in Western Saudi Arabia.

Introduction: Various drug-food interactions exist that may hinder treatment and can sometimes be lethal. Our aim was to assess the level of public knowledge and awareness in Jeddah city, Western Saudi Arabia, about drug-food interactions, along with the effects of demographics on their knowledge. Methods: A survey questionnaire was administered in this cross-sectional study to participants spread across multiple locations in Jeddah, including in malls and public gatherings. Participants included both males and females. Sample size was calculated through Raosoft® software. Data analysis was executed using IBM Statistic SPSS and the level of statistical significance was set at p < 0.05. Results: A total of 410 people participated in the study and only 92.68% (380) of responses were enrolled in the study; 7.32% (30) were not enrolled due to the exclusion criteria. Surprisingly, only six out of eighteen questions regarding drug-food interactions in the administered questionnaire were correctly answered by 380 participants. Data indicated that the participants had a poor to intermediate level of both knowledge and awareness with respect to drug-food interactions. Furthermore, participants showed moderate to strong awareness of the effects of alcohol and tea generally, and their interaction with medication. Conclusion: Participants in our study showed inadequate knowledge of basic and fundamental information about drug-food interactions, which highlights the dire need to increase awareness.

Mild hyperthermia prior to electroporation increases transfection efficiency in HCT 116, HeLa S3 and SGC 7901 cells.

The change in transfection efficiency of electroporation by the combined treatment with mild preheating (40 degrees C for 30 min) was investigated. HCT 116, HeLa S3 and SGC 7901 cells were treated with electroporation in medium containing pBKCMV-Luc plasmid with or without preheating. After 24 h, luciferase activity was increased by 36, 28 and 77%; luciferase mRNA transcription was increased by 45, 50 and 68%; and fluorescein isothiocyanate-dextran accumulation was increased by 9, 35 and 15% in preheated groups, respectively. These results demonstrate that the transfection efficiency was enhanced by mild preheating. The mechanism partially involves increased macromolecular particle accumulation.

Achieving better quality care in general practice: are incentives the answer?

BACKGROUND: The introduction of financial incentives, such as the quality and outcomes framework (QOF), historically lead to improvements in standardising practice. However, with shifting demands on healthcare providers, are these schemes still enough to drive high-quality care? AIM: To explore current incentives, intrinsic and extrinsic, their role and effectiveness in improving quality of care and how they are perceived by GPs. METHOD: Mixed methods study using two systematic literature reviews including 44 papers and 18 semi-structured interviews with GPs. RESULTS: In the literature, QOF was associated with reduced socioeconomic inequalities, decreased mortality and improved outcomes. However, the absence of control groups and the simultaneous analysis of multiple indicators complicates the findings. GPs agreed with the literature and viewed financial incentives as beneficial, however, they felt the key driver in providing good-quality care was their intrinsic motivation. Financial incentives were found to contribute to depersonalised care, diluted provision of non-incentivised activities and hindered overall practice. The results from the second literature review were in keeping with the views of the participants. They illustrated the importance of managing factors contributing to physician burnout, reduced performance, and low job satisfaction, which can result in the provision of low-quality care. CONCLUSION: Financial incentives have the potential to induce behaviour change, however, their use in quality improvement is limited when used alone. If used in an environment that nurtures intrinsic motivation, healthcare providers will be more driven to achieve a higher quality of care and will be better able to cope with shifting demands.

Design, synthesis, and biological evaluation of artificial macrosphelides in the search for new apoptosis-inducing agents.

Various artificial macrosphelides were designed and synthesized, including ring-enlarged analogues and epothilone-hybrid compounds. Syntheses were accomplished in an efficient manner by using a ring-closing metathesis (RCM) strategy in a key macrocyclization step. Biological evaluation of these new macrosphelide-based derivatives revealed that several epothilone hybrids, in which a thiazole-containing side chain was incorporated, exhibited potent apoptosis-inducing activity toward human lymphoma cells. These activities were considerably enhanced relative to those of natural macrosphelide compounds. Structure-activity relationship studies revealed that the "ene-dicarbonyl" substructure is apparently essential for bioactivity.

Modulation of activation-induced cytidine deaminase by curcumin in Helicobacter pylori-infected gastric epithelial cells.

BACKGROUND: Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori-infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-kappaB activation by H. pylori and hence, inhibition of NF-kappaB pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-kappaB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-kappaB inhibitory activity in H. pylori-infected gastric epithelial cells. MATERIALS AND METHODS: MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-kappaB, inhibitors of NF-kappaB (IkappaB), and IkappaB kinase (IKK) complex regulation with or without curcumin. RESULTS: The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (< or =10 micromol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-kappaB activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (< or =10 micromol/L) has suppressed H. pylori-induced NF-kappaB activation via inhibition of IKK activation and IkappaB degradation. CONCLUSION: Nonbactericidal concentrations of curcumin downregulated H. pylori-induced AID expression in gastric epithelial cells, probably via the inhibition of NF-kappaB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori-related gastric carcinogenesis.

Effect of resveratrol on Helicobacter pylori-induced interleukin-8 secretion, reactive oxygen species generation and morphological changes in human gastric epithelial cells.

Inflammatory cytokine interleukin-8 (IL-8) and reactive oxygen species (ROS) overexpressed in the gastric mucosa when exposed to Helicobacter pylori, defined as a class I carcinogen. Moreover, infection with H. pylori leads to morphological changes in co-cultured cells known as hummingbird phenomenon along with increased motility. Resveratrol, a highly abundant polyphenol in red grapes, has shown anti-inflammatory, anti-cancer, cardioprotective and neuroprotective activities. However, the effect of resveratrol in H. pylori-infected cells has not been investigated. The present study was, therefore, aimed to evaluate the effect of resveratrol on the induction of IL-8, ROS and hummingbird morphology in H. pylori-infected gastric epithelial cells. The non-toxic concentration of resveratrol for both H. pylori and epithelial cells was determined by brucella broth dilution method and DNA fragmentation assay. The non-toxic resveratrol (< or =100 microM) treatment did not demonstrate any inhibitory effect against H. pylori adhesion to gastric epithelial cells. However, preincubation of the cells with 75 and 100 muM of resveratrol significantly (p<0.05 and p<0.01 respectively) inhibited the secretion of IL-8 from H. pylori-infected cells. In addition, resveratrol pretreatment at 1-100 muM suppressed H. pylori-induced ROS generation in a concentration dependent manner. Moreover, H. pylori-initiated morphological changes were markedly blocked by resveratrol. Hence, resveratrol can be considered as a potential candidate against various H. pylori related gastric pathogenic processes.

Potential proapoptotic phytochemical agents for the treatment and prevention of colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of mortality among men and women. Chemo-resistance, adverse effects and disease recurrence are major challenges in the development of effective cancer therapeutics. Substantial literature on this subject highlights that populations consuming diets rich in fibers, fruits and vegetables have a significantly reduced incidence rate of CRC. This chemo-preventive effect is primarily associated with the presence of phytochemicals in the dietary components. Plant-derived chemical agents act as a prominent source of novel compounds for drug discovery. Phytochemicals have been the focus of an increasing number of studies due to their ability to modulate carcinogenic processes through the alteration of multiple cancer cell survival pathways. Despite promising results from experimental studies, only a limited number of phytochemicals have entered into clinical trials. The purpose of the current review is to compile previously published pre-clinical and clinical evidence of phytochemicals in cases of CRC. A PubMed, Google Scholar and Science Direct search was performed for relevant articles published between 2008-2018 using the following key terms: 'Phytochemicals with colorectal cancers', 'apoptosis', 'cell cycle', 'reactive oxygen species' and 'clinical anticancer activities'. The present review may aid in identifying the most investigated phytochemicals in CRC cells, and due to the limited number of studies that make it from the laboratory bench to clinical trial stage, may provide a novel foundation for future research.