• Toxicological Research
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• v.33 no.1
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• pp.1-5
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• 2017

Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.222-230
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• 2007

Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. Nitrofurantoin (NF) is clinical chemotherapeutic agent and antimicrobial and used to treatment of urinary tract infections. However, NF has been shown to result in pulmonary toxic effects. In this research, we revealed the changing expression gene profiles in BEAS-2B, human bronchial epithelial cell line, exposed to NF by using human oligonucleotide chip. Through the clustering analysis of gene expression profiles, we identified 136 up-regulated genes and 379 down-regulated genes changed by more than 2-fold by NF. This study identifies several interesting targets and functions in relation to NF-induced toxicity through a gene ontology analysis method including biological process, cellular components, molecular function and KEGG pathway.

• BMB Reports
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• v.36 no.3
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• pp.269-274
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• 2003

In the fight against cancer, novel chemotherapeutic agents are constantly being sought to complement existing drugs. Various studies have presented evidence that the apoptosis that is induced by these anticancer agents is implicated in tumor regression, and Bcl-2 family genes play a part in apoptosis following treatment with various stimuli. Here, we present data that a styrylpyrone derivative (SPD) that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt-mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting and immunostaining revealed up-regulation of the proapoptotic Bax protein expression. SPD, however, did not affect the expression of the anti-apoptotic protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.445-453
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• 2016

Epidermal growth factor receptors (EGFRs/HERs) and downstream signaling pathways have been implicated in the pathogenesis of several malignancies including breast cancer and its resistance to treatment with chemotherapeutic drugs. Consequently, several monoclonal antibodies as well as small molecule inhibitors targeting these pathways have emerged as therapeutic tools in the recent past. However, studies have shown that utilizing these molecules in combination with chemotherapy has yielded only limited success. This review describes the current understanding of EGFRs/HERs and associated signaling pathways in relation to development of breast cancer and responses to various cancer treatments in the hope of pointing to improved prevention, diagnosis and treatment. Also, we review the role of breast cancer stem cells (BCSCs) in disease and the potential to target these cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6535-6539
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• 2015

This study was designed to assess, whether a new chemotherapeutic microtubule inhibitor, Epothilone B (EpoB, Patupilone), can induce DNA damage in normal ovarian cells (MM14.Ov), and to evaluate if such damage could be repaired. The changes were compared with the effect of paclitaxel (PTX) commonly employed in the clinic. The alkaline comet assay technique and TUNEL assay were used. The kinetics of DNA damage formation and the level of apoptotic cells were determined after treatment with IC50 concentrations of EpoB and PTX. It was observed that PTX generated significantly higher apoptotic and genotoxic changes than EpoB. The peak was observed after 48 h of treatment when the DNA damage had a maximal level. The DNA damage induced by both tested drugs was almost completely repaired. As EpoB in normal cells causes less damage to DNA it might be a promising anticancer drug with potential for the treatment of ovarian tumors.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.3 no.1
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• pp.84-88
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• 2000

Secondary peptic ulceration and gastritis have been known to be associated with stress, exogenous agents, drugs or infection. Salicylate (aspirin) ingestion has been known to be associated with increased incidence of gastric ulcer and more frequently as the cause of hemorrhagic gastric erosions and gastritis. Some medications such as tetracyclines and iron preparations have been associated with ulceration of the gastrointestinal tract. Chemotherapeutic agents including cytoxan and methotrexate also have been implicated in the development of mucosal and gastrointestinal ulcers. We have experienced two cases of hemorrhagic gastric ulcers due to creosote ingestion in a 13 month and a 5 year old boys. Creosote is a main component of one of the popular digestives, Jungrohwan in Japan and Korea.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.287-290
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• 2007

Intrinsic or acquired resistance to chemotherapeutic drugs is one of the major obstacles to effective cancer treatment. Hypoxia is widespread in solid tumors as a consequence of decreased blood flow in the tumor-derived neovasculature. The recent finding of a link between hypoxia and chemoresistance prompted us to investigate whether hypoxia induces doxorubicin resistance in human MCF-7 breast cancer cells. Low oxygen concentration decreased the doxorubicin sensitivity in MCF-7 cells. The expression of p-glycoprotein, a major MDR-related transporter, and those of apoptosis-related proteins (anti-apoptotic Bcl-2, Bcl-XL and pro-apoptotic Bax) were not altered by hypoxia in MCF-7 cells. Intracellular uptake of doxorubicin was significantly decreased under hypoxic conditions. Decreased cellular uptake of doxorubicin under hypoxia may contribute to causing doxorubicin resistance in these cells. The use of agents that can modulate the doxorubicin uptake for adjuvant therapy may contribute to improving the therapeutic efficacy of doxorubicin in breast cancer patients.

• Bulletin of the Korean Chemical Society
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• v.28 no.11
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• pp.1931-1938
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• 2007

Analyzed are recent advances in design of novel boronared conjugates of synthetic and natural porphyrins and chlorins. These compounds showed high efficacy as cytotoxic agents for tumor cells in culture and as phototoxins in photodynamic therapy of tumor xenografts. Thus, boronated porphyrins and chlorins emerge as promising class of anticancer agents with potentially multiple advantages: the chemotherapeutic drugs alone and photo- and radiosensitizers in binary treatments.

• Molecules and Cells
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• v.44 no.5
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• pp.356-362
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• 2021

An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. In addition, changes in the gut microbiota are known to be involved in the antitumor immune response as well as the modulation of the intestinal immune system. As a result, the gut microbiota plays an important role in modulating the efficacy of immune checkpoint inhibitors. Therefore, gut microbiota could be considered as an adjuvant treatment option with other cancer treatment or as another marker for predicting treatment response. In this review, we examine how gut microbiota affects cancer treatments.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.525-533
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• 1997

Background : No ideal combination chemotherapy for lung cancer has been established even though lots of combination anticancer chemotherapies have been tried. For the combination of anticancer drugs, the interaction of anticancer drugs is very important but unpredictable factor. In this experiment, we designed and tested new experiment to measure the interaction of two anticancer drugs using MIT assay in an attempt to predict clinical response of the combination regimen. Methods : With human lung adenocarcinoma cell line (PC-14), the cytotoxic effect of cisplatin, adriamycin, mitomycin C and etoposide were measured by in vitro chemosensitivity test (MIT assay). The combined cytotoxic effects of combination of two drugs were also measured in every combination of the drug concentrations and analyzed the interaction by Anava analysis of two way factorial design. Results : Four individual drugs showed cytotoxic effects on PC-14 by dose dependent fashion. Comparison of two drug combinations revealed that mitomycin C + cisplatin and adriamycin + cisplatin combinations showed stronger synergistic cytotoxic effects. Conclusion : From this experiment, we suggest two combinations of mitomycin C + cisplatin and adriamycin + cisplatin as chemotherapeutic regimens for unresectable non-small cell lung cancer. Furthermore, this experimental design could be applied to other types of cancer requiring combination anticancer chemotherapy.