• Biomolecules & Therapeutics
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• 제26권1호
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• pp.29-38
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• 2018

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3091-3096
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• 2015

Worldwide, breast cancer is the most common malignant neoplasm and the second most common cause of cancer death in women. This malignancy is recognized to be estrogen-dependent and due to this feature, hormone replacement therapy is regarded as potentially dangerous in breast cancer survivors who seek relief of their menopausal symptoms. Whereas hot flashes are detected in nearly half of postmenopausal women with a relatively high frequency and severity, botanic sources of estrogens have been proposed as an alternative treatment. Nevertheless, estrogenic properties of these compounds suggest possibility of stimulating cancer recurrence or worsening prognosis in survivors. As well, effects in improving vasomotor climacteric changes is controversial. Many studies have considered the subject, some focusing on efficacy of phytoestrogens for control of menopausal symptoms, and others discussing effects of these compounds on breast cancer outcome in terms of survival or recurrence. The present article is a concise review of the effects of consumption of phytoestrogens on menopausal symptoms, namely hot flashes, and breast cancer recurrence and mortality in survivors of the disease. Overall, the major part of the current existing literature is in favor of positive effects of phytoestrogens on breast cancer prognosis, but the efficacy on menopausal symptoms is probably minimal at the best.

• BMB Reports
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• 제45권1호
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• pp.51-56
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• 2012

The purpose of this study was to determine the effects of duration and timing of glucocorticoid treatment on the expansion and differentiation of porcine neonatal pancreas cell clusters (NPCCs) into ${\beta}$-cells. After transplantation of NPCCs, the ductal cyst area and ${\beta}$-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3${\beta}$ gene expression was significantly downregulated following Dx treatment, whereas PGC-1${\alpha}$ expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into ${\beta}$-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1${\alpha}$ plays an important role in the expansion and transdifferentiation of porcine NPCCs, and the initial 2 weeks following transplantation of porcine NPCCs is a critical period in determining the final ${\beta}$-cell mass in grafts.

• Molecules and Cells
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• 제37권12호
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• pp.888-898
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• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2923-2933
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• 2016

Recently, we reported an inverse association between high 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South America) and breast cancer (BC) risk. Stronger inverse associations were found in high strata of tea, vegetable, fruit and energy intakes, and in overweight/obese women, suggesting possible roles for 'mate' mainly from its antioxidant contribution. The present study attempted to thoroughly explore possible associations among 'mate' and tea intake, dietary antioxidants and BC risk. Combining two databases of previous studies, 572 BC incident cases and 889 controls were interviewed with a specific questionnaire featuring socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire (64 items), focusing on 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit). Food-derived nutrients were calculated from available databases. Odds ratios (OR) and their 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest 'mate' intake was significantly inversely associated with BC risk for both low and high carotenoids (OR=0.40 vs. 0.41), vitamin C (OR=0.33 vs. 0.50), vitamin E (OR=0.37 vs. 0.45), flavonols (OR=0.38 vs. 0.48) and reduced glutathione (OR=0.48 vs. 0.46) strata. High tea intake showed significant inverse risk associations only with high carotenoids (OR=0.41), vitamin E (OR=0.48) and reduced glutathione (OR=0.43) strata. In conclusion, a strong and inverse association for 'mate' intake and BC was found, independent of dietary antioxidant levels. Also strong inverse associations with tea intake were more evident only at high levels of certain dietary antioxidants.

• Biomolecules & Therapeutics
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• 제20권5호
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• pp.470-476
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• 2012

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.

• 혜화의학회지
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• 제19권1호
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• pp.25-34
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• 2010

Background : The human being and the bacteria have accomplished a balance and have coexisted each other during long time. Probiotics have evolved with the human host to exist and the result they have operated profitably to human host. So it requires that the functions of probiotics are expounded in view of Traditional Korean Medicine. Aim : Suggest the functions of probiotics in view of Traditional Korean Medicine. Method : The author's research has been performed to review the related references. Results : Probiotics assist the absorption of the lactose, proteins and minerals and product several kinds of vitamins, organic acids. Probiotics suppresses the growth of noxious bacteria and the production of harmful substances or gases. They absorbed and discharge the bile acid, and thus help us maintain the optimal level of blood cholesterol concentration. They can reinforce the immune response of the mucous membrane and control the hypersensitivity immune reaction such as asthma, atopy on the other hand. Probiotics have right functions as above and so can be applied widely in treatment of various disease and symptom. Conclusion : Considering the functions of probiotics in view of Traditional Korean Medicine, they participate in our spleen-earth-system (digestion and synthesis) and liver-wood-system (regulation of digestion, metabolism, internal secretion etc.), assist the function of lung-metal system(respiration and regulation of water metabolism) and regulate wi-chi (reinforce/control immune system). Consequently, hereafter there would be a necessity of control a circumstance in treatment of various diseases under these categories that probiotics should be able to do their right functions inside the human body.

• 종양간호연구
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• 제11권1호
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• pp.20-25
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• 2011

Purpose: The study was aimed to review and understand the meaning of cancer cachexia. Methods: Using the keywords "cachexia" and "cancer cachexia" 30 oncology research published from 1974 to 2009 were selected for the review. Results: The mechanism of cancer cachexia has not been fully understood, but various pathogenesis appears to be involved in the development cachexia including altered metabolism of carbohydrate, lipid, and protein associated with cytokines and hormone. As a result, muscle strength, food intake and resting energy expenditure (REE) are reduced. Most medications for the treatment of cachexia show debating results except some drugs such as megace. Supportive care including nutritional education, nursing care, and social support are found another effective treatment options. Conclusion: The results of this study would help oncology nurses to understand the mechanism of cancer cachexia and its management.

• BMB Reports
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• 제46권9호
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• pp.429-438
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• 2013

Aging is the strongest risk factor for cancer development, suggesting that molecular crosstalks between aging and tumorigenesis exist in many cellular pathways. Recently, Sirtuins (Sirt1-7), the mammalian homologues of aging-related $sir2{\alpha}$ in yeast, have been shown to modulate several major cellular pathways, such as DNA repair, inflammation, metabolism, cell death, and proliferation in response to diverse stresses, and may serve as a possible molecular link between aging and tumorignenesis. In addition, growing evidence suggests that sirtuins are directly implicated in the development of cancer, and they can act as either a tumor suppressor or promoter, depending on the cellular context and tumor types. While the functions of Sirt1 in tumorigenesis have been reported and reviewed in many studies, the connection between sirtuins 2-7 and the development of cancer is less established. Thus, this review will present the recent updates on the emerging roles of Sirt2-7 members in carcinogenesis.

• BMB Reports
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• 제54권1호
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• pp.12-20
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• 2021

In the last decade, we have witnessed an unprecedented clinical success in cancer immunotherapies targeting the programmed cell-death ligand 1 (PD-L1) and programmed cell-death 1 (PD-1) pathway. Besides the fact that PD-L1 plays a key role in immune regulation in tumor microenvironment, recently a plethora of reports has suggested a new perspective of non-immunological functions of PD-L1 in the regulation of cancer intrinsic activities including mesenchymal transition, glucose and lipid metabolism, stemness, and autophagy. Here we review the current understanding on the regulation of expression and intrinsic protumoral activity of cancer-intrinsic PD-L1.