Dynamics of Keratinocytes in Vivo using 2H2O Labeling: A Sensitive Marker of Epidermal Proliferation State

Hsieh, Elaine; Chai, Christine M.; Lumen, Benito O. de; Neese, Richard A.; Hellerstein, Marc K.

doi:10.1111/j.0022-202x.2004.23303.x

Cited by 48 publications

(35 citation statements)

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“…If some of the health benefits of CR can be reproduced, including reduction in cancer promotion, this might be a therapeutic strategy worth pursuing. Human CR studies using the techniques described here [e.g., proliferation of skin cells, T cells and mammary epithelial cells (17,32,34)] could, in principle, be performed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…The skin was rinsed with phosphate buffer solution (PBS; GIBCO, Grand Island, NY), divided into three smaller pieces, immersed in dispase II (Roche, Indianapolis, IN), and incubated for 3.5 h at 37°C on a shaker. The epidermis was then peeled from the dermis in thin white sheets, as described previously (17).…”

Section: Epidermal Cell (Keratinocyte) Isolationmentioning

confidence: 99%

“…This technique has a number of advantages over 3 HdT and BrdU labeling (34,35) and has been used to measure turnover of keratinocytes, mammary epithelial cells, T cells, adipocytes, colonocytes, leukemic cells, and other cells (6,16,17,21,30,32,39,40). This technique is highly reproducible and simple to apply, thereby allowing numerous groups or hypotheses to be tested at a relatively high throughput.…”

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confidence: 99%

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Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding

Hsieh¹,

Chai²,

Hellerstein³

2005

American Journal of Physiology-Endocrinology and Metabolism

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Reduced cell proliferation may mediate anticarcinogenic effects of caloric restriction (CR). Using heavy water ( 2 H2O) labeling, we investigated the cell proliferation response to CR in detail, including time course, effect of refeeding, and role of intermittent feeding with 5% CR. In the time-course study, 8-wk-old female C57BL/6J mice were placed on a 33% CR regimen (fed 3 times/wk) for varying durations. Compared with responses in controls fed ad libitum (AL), proliferation rates of keratinocytes, mammary epithelial cells, and T cells were markedly reduced within 2 wk of CR. In mice fed 95% ad libitum (C95, fed 3 times/wk), cell proliferation was also reduced in all tissues so that differences from 33% CR were only significant at 1 mo. In the refeeding study, mice were refed a C95 diet for varying durations after 1 mo of 33% CR. Cell proliferation rebounded to a suprabasal rate in all tissues after 2 wk of refeeding and then normalized after 2 mo, although the C95 group again exhibited lower cell proliferation than the AL group. The role of intermittent feeding was studied by comparing 33% CR and C95 animals (both fed intermittently) with animals fed isocalorically either daily or continuously by pellet dispenser. Intermittent feeding had no additive effect on 33% CR but reduced cell proliferation in all tissues at the 95% caloric intake level. In summary, the CR effect on cell proliferation is potent, rapid, and reversible in several tissues, and an intermittent feeding pattern reproduces much of the effect in the absence of substantial CR. stable isotopes; refeeding; keratinocyte; mammary; T cell CALORIC RESTRICTION (CR), defined as undernutrition without malnutrition (45), was first discovered in 1935 to extend maximal life span in rats (29). Since then, similar findings have been reported in mice, fish, flies, worms, and yeast (45). A range of 30 -70% extension of maximal life span has been achieved using variations on CR regimens (45), including both early-and adult-onset CR (44,46). CR also exerts a number of other beneficial health effects, including reduced carcinogenesis, enhanced insulin sensitivity, and reduced cardiovascular disease risk (15). The inhibitory effect of CR on carcinogenesis is of particular interest, because CR effectively inhibits spontaneous tumor formation as well as neoplasias in knockout/ transgenic models of cancer-and chemically induced tumorigenesis (18,19,45). The mechanisms by which CR extends life span and inhibits carcinogenesis remain unknown (15,19).CR could affect several steps in the multistage carcinogenesis model (18). CR may function as an anti-initiator by decreasing carcinogen activation, enhancing carcinogen detoxification, scavenging reactive oxygen species, or enhancing DNA repair (18). CR could also function as an antipromoter by reducing mitoses of initiated cells, altering expression of cancer-related genes, decreasing inflammation, enhancing immune competence, or stimulating apoptosis (18). Reductions in cell proliferation might be expected in view of ob...

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Section: Discussionmentioning

confidence: 99%

Section: Epidermal Cell (Keratinocyte) Isolationmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding

Hsieh¹,

Chai²,

Hellerstein³

2005

American Journal of Physiology-Endocrinology and Metabolism

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“…In human leukemia L1210 cells, lunasin was able to reduce cell proliferation and induce apoptosis (40,41). Similarly, in DMAB-induced mouse skin tumors, lunasin was able to decrease the number of tumors generated and delay the generation of tumors in skin (42,43). Therefore, lunasin has been identified as a promising polypeptide for preventing tumor formation induced by chemical carcinogens.…”

Section: Molecular Mechanisms Of Lunasin In the Prevention And Treatmmentioning

confidence: 99%

Lunasin: A promising polypeptide for the prevention and treatment of cancer

et al. 2017

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Abstract. Strategies for the treatment of cancer remain unsatisfactory due to the poor understanding of the complicated underlying molecular mechanisms of carcinogenesis. A number of types of cancer exhibit a marked association with dietary habits and lifestyles. Therefore, the modulation of dietary habits or lifestyles may be an effective strategy for preventing the formation and progression of cancer. Proteins and polypeptides from soybean have been developed as healthcare products due to their marked activity in inhibiting the progression of cancer at various stages. Lunasin, containing 43 amino acid residues, is one such example of a soybean-derived polypeptide that has been demonstrated to exhibit marked anti-cancer activity. In the present review, studies of the underlying molecular mechanisms and potential advantages of lunasin in the prevention and treatment of cancer have been examined, to provide a theoretical reference for the development of natural product-based agents or healthcare products for the prevention and treatment of cancer. IntroductionCancer is well-known to be one of the leading causes of mortality worldwide (1). However, the therapy of various types of cancer remains unsatisfactory due to the poor understanding of the complicated underlying molecular mechanisms of carcinogenesis. A number of epidemiological studies have demonstrated that a number of types of cancer exhibit a marked association with dietary habits and lifestyles (2-4). A statistical study has demonstrated that ~3.07 million individuals in China were diagnosed with cancer in 2012, which accounts for 1/5 of the total number of patients with cancer worldwide (5). Furthermore, ~2.21 million patients succumbed to cancer in China, which is ~25% of the total mortality worldwide due to cancer (5). Epidemiological evidence has demonstrated that cancer in 35% of patients exhibits a marked association with lifestyle, particularly diet (2). Therefore, the adjustment of dietary habits and lifestyles may be an effective strategy to prevent carcinogenesis. Cancer cell-and tumor-bearing animal models have demonstrated that the consumption of foods containing natural compounds with anti-cancer activity is able to markedly reduce the risk of cancer, and increase the sensitivity of cancer cells to treatment (6). A number of phytochemicals, including resveratrol, quercetin and flavonoids, have been demonstrated to exhibit marked anti-cancer activity (7-9). Similarly, foodborne proteins and polypeptides have attracted attention due to their specific advantages as anti-cancer substances (10,11). Compared with certain small-molecule drugs, polypeptides exhibit characteristics of increased affinity, marked ability of specific targeting and decreased toxicity; furthermore, polypeptides exhibit increased permeability in tissues compared with protein-based drugs (12). Therefore, polypeptides have been recognized as potential natural anti-cancer substances for inhibiting the development and progression of cancer at different stages (13).Following ...

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“…This 43-amino acid peptide is found in soy, wheat, barley, and other seeds (Hernandez-Ledesma et al 2009) and is a chemopreventive agent against oncogenes and chemical carcinogens (Ortiz-Martinez et al 2014). With an adequate bioavailability following oral administration, lunasin was shown to prevent skin cancer in a mouse model induced by chemical carcinogens (Galvez et al 2001;Hsieh et al 2004). An epigenetic mechanism of action proposed for this peptide is the selective killing of newly transformed cancer cells by acting as a histone acetyltransferase (HAT) inhibitor and repressing cell cycle progression (Hernandez-Ledesma et al 2009).…”

Section: Targeting Cancer Cells Using Natural Peptidesmentioning

confidence: 99%

Anticancer Peptides: Prospective Innovation in Cancer Therapy

Gaspar

Castanho

2016

Host Defense Peptides and Their Potential as Therapeutic Agents

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Current cancer treatments require improvements in selectivity and efficacy. Surgery, radiation, and chemotherapy approaches result in patient's suffering over time due to the development of severe side-effects that simultaneously condition adherence to therapy. Biologically active peptides, in particular antimicrobial peptides (AMPs), are versatile molecules in terms of biological activities. The cytotoxic activities of several AMPs turn this group of molecules into an amazing pool of new templates for anticancer drug development. However, several unmet challenges limit application of peptides in cancer therapy. The mechanism(s) of action of the peptides need better description and understanding, and innovative targets have to be discovered and explored, facilitating drug design and development. In this chapter, we explore the natural occurring AMPs as potential new anticancer peptides (ACPs) for cancer prevention and treatment. Their modes of action, selectivity to tumor compared to normal cells, preferential targets, and applications, but also their weaknesses, are described and discussed.

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Dynamics of Keratinocytes in Vivo using 2H2O Labeling: A Sensitive Marker of Epidermal Proliferation State

Cited by 48 publications

References 48 publications

Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding

Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding

Lunasin: A promising polypeptide for the prevention and treatment of cancer

Anticancer Peptides: Prospective Innovation in Cancer Therapy

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