Stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Research data show that more resistant stem cells than common cancer cells exist in cancer patients.To identify unrecognized differences between cancer stem cells and cancer cells might be able to develope effective classification,diagnose and treat ment for cancer.

Stem Cells,Cancer and Cancer Stem Cells

Reactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals (·OH), alkoxyl radicals, superoxide anion (O2·−), singlet oxygen (1O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules. Cancer cell death types induced by ROS include apoptotic, autophagic, ferroptotic and necrotic cell death. Since abnormal metabolism in cancer cells, they have higher ROS content compared to normal cells. The higher endogenous ROS levels in cancer cells endow them more susceptible to the ROS-induction treatment. Indeed, some anticancer drugs currently used in clinic, such as molecular targeted drugs and chemotherapeutic agents, effectively kill cancer cells by inducing ROS generation. In addition, photodynamic therapy (PDT) is mainly based on induction of ROS burst to kill cancer cells. The mechanism of cell death induced by radiotherapy using ionizing radiation also refers to ROS production. Moreover, ROS play an important role in tumor immune therapy. Altogether, combining above traditional treatments with ROS-induced agents will be considered as a promising strategy in cancer therapy. In this review, we focus on our current understanding of the anticancer effects of ROS.

Induction of reactive oxygen species: an emerging approach for cancer therapy.

Mycotoxins are toxic substances that can infect many foods with carcinogenic, genotoxic, teratogenic, nephrotoxic, and hepatotoxic effects. Mycotoxin contamination of foodstuffs causes diseases worldwide. The major classes of mycotoxins that are of the greatest agroeconomic importance are aflatoxins, ochratoxins, fumonisins, trichothecenes, emerging Fusarium mycotoxins, enniatins, ergot alkaloids, Alternaria toxins, and patulin. Thus, in order to mitigate mycotoxin contamination of foods, many control approaches are used. Prevention, detoxification, and decontamination of mycotoxins can contribute in this purpose in the pre-harvest and post-harvest stages. Therefore, the purpose of the review is to elaborate on the recent advances regarding the occurrence of main mycotoxins in many types of important agricultural products, as well as the methods of inactivation and detoxification of foods from mycotoxins in order to reduce or fully eliminate them.

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Advances in Occurrence, Importance, and Mycotoxin Control Strategies: Prevention and Detoxification in Foods.

This present review described the validation method of in-vitro bioassay for its application in herbal drug research. Seven sequencing steps that can be taken for performing a valid bioassay include: literature survey, sample stability evaluation, Biosystem performance testing, Sample performance evaluation, determination of 50% effective concentration or cytotoxic concentrations, selective index evaluation, and determination of accurate relative potency of sample. Detailed methods and acceptance criteria for each step are described herein. Method calculations of the relative potency of sample using European Pharmacopeia 10.0, 5.3 (2020) were recommended instead of using United States Pharmacopeia 42 (2019). For having reliable data and conclusions, all methods (chemical and bioassay) need to be first validated before any data collection. Absence of any validation method may results in incorrect conclusions and bias.

Validation of in-vitro bioassay methods: Application in herbal drug research.

By simultaneously amplifying more than one locus in the same reaction, multiplex PCR is becoming a rapid and convenient screening assay in both the clinical and the research laboratory. While numerous papers and manuals discuss in detail conditions influencing the quality of PCR in general, relatively little has been published about the important experimental factors and the common difficulties frequently encountered with multiplex PCR. We have examined various conditions of the multiplex PCR, using a large number of primer pairs. Especially important for a successful multiplex PCR assay are the relative concentrations of the primers at the various loci, the concentration of the PCR buffer, the cycling temperatures and the balance between the magnesium chloride and deoxynucleotide concentrations. Based on our experience, we propose a protocol for developing a multiplex PCR assay and suggest ways to overcome commonly encountered problems.

Multiplex PCR: Critical Parameters and Step-by-Step Protocol

Preventing food from fungal infestation has become a cause of great concern as food safety is of particular importance to public health globally. Recently International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in its 2016 press release has urged to take action against widespread mycotoxin contamination in developing countries. Deoxynivalenol (DON) is a group B trichothecene mycotoxin, produced by common field pathogens such as Fusarium graminearum and Fusarium culmorum, and reported to be the predominant contaminant of food commodities. At present, no detailed/systematic review regarding the global occurrence of DON in various food and grain samples is available in the literature. Considering DON's cosmopolitan behavior and toxicological manifestations, the present review summarizes the region-wise reports and surveys conducted across the globe during the last decade, on the occurrence of DON in the food commodities intended for human consumption. Studies conducted on DON metabolites either in food, urine or blood samples from humans have also been reviewed. The present review indicates that the current exposure levels of DON might pose a health risk for the consumers, especially in growing children, necessitating to take vigilant steps to guarantee food safety.

Global occurrence of deoxynivalenol in food commodities and exposure risk assessment in humans in the last decade: a survey.

The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate-binding cassette transporter in multidrug resistance cells and interferes with Akt signaling pathway, Wnt/β-catenin, Hedgehog, and Notch pathways of cancer progression. Salinomycin selectively targets cancer stem cells. The potential of salinomycin to eliminate both cancer stem cells and therapy-resistant cancer cells may characterize the compound as a novel and an efficient chemotherapeutic drug.

https://journals.sagepub.com/doi/pdf/10.1177/1010428317695035

Salinomycin: A new paradigm in cancer therapy.

Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We further evaluated the molecular mechanism behind SAL and RES mediated cell death. Cytotoxicity assay was performed to determine 50% inhibitory concentration (IC50) of SAL and RES in different human breast cancer cells (HBCCs). Drug synergism and combination index (CI) were calculated using CompuSyn software and effects of synergistic combinations (CI < 1) involving lower doses of SAL and RES were selected for further studies. This combination significantly induced apoptosis in HBCCs without affecting non tumorigenic human breast epithelial cells MCF-10A. Co-treatment enhanced apoptosis in MCF-7 cells via reactive oxygen species (ROS) mediated mitochondrial dysfunction. Oxidative stress disrupt redox homeostasis which altered antioxidant enzymes viz. CuZn Superoxide dismutase (SOD), MnSOD and catalase. Additionally, combination altered nuclear morphology, enhanced PARP cleavage and led to caspase activation. SAL and RES also synergistically modulated MAPK pathway. Study suggests that SAL and RES offer a novel combination approach for the treatment of breast cancer.

Novel combination of salinomycin and resveratrol synergistically enhances the anti-proliferative and pro-apoptotic effects on human breast cancer cells.

Sonal Srivastava

Papers

Global occurrence of deoxynivalenol in food commodities and exposure risk assessment in humans in the last decade: a survey.

Salinomycin: A new paradigm in cancer therapy.

Novel combination of salinomycin and resveratrol synergistically enhances the anti-proliferative and pro-apoptotic effects on human breast cancer cells.

Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo.

Chetomin induces apoptosis in human triple-negative breast cancer cells by promoting calcium overload and mitochondrial dysfunction.