Dietary calcium supplementation increases apoptosis in the distal murine colonic epithelium

Penman, Ian; Liang, Qianwa; Bode, John; Eastwood, M. A.; Arends, Mark J.

doi:10.1136/jcp.53.4.302

Cited by 35 publications

(30 citation statements)

References 40 publications

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“…In agreement with studies using animal models and cell culture (12,13), our results support a mechanism in which calcium and vitamin D reduce the risk of colorectal cancer by increasing the level of apoptosis in the colorectal epithelium. However, for calcium, the positive association was stronger in patients with adenomas, whereas for vitamin D, the association was stronger in adenoma-free patients.…”

Section: Discussionsupporting

confidence: 80%

“…Animal models and cell culture have provided evidence that these micronutrients may act by influencing apoptosis. For example, compared with mice on a standard diet of 0.5% calcium, increasing the concentration to 1.0% resulted in higher levels of apoptosis in the distal colorectal epithelium (12). In human colorectal adenoma and cancer cell lines, the active metabolite of vitamin D [1,25 (OH) 2 D 3 ] was found to induce apoptosis in a dose-dependent manner (13).…”

Section: Introductionmentioning

confidence: 99%

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Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium

Miller¹,

Keku

Satia

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: Decreased apoptosis in the colon is potentially an early indicator of colon cancer risk and may be influenced by calcium and vitamin D. This report describes the associations of calcium intake and 25-hydroxyvitamin D levels with apoptosis in colorectal epithelium. Methods: Consecutive patients undergoing colonoscopies were recruited for a study designed to examine risk and etiologic factors for colorectal adenomas. Diet was assessed by food frequency questionnaire, and in one subpopulation, serum 25-hydroxyvitamin D levels were measured using an enzyme immunoassay. Apoptosis was scored from normal rectal mucosal pinch biopsies. Linear and logistic regression analyses were used to examine associations between calcium, serum vitamin D, and apoptotic scores. Data were available for 498 and 280 patients for the calcium and vitamin D analyses, respectively.Results: Associations of calcium intake and vitamin D with apoptosis were modified by adenoma case-status. In an adjusted logistic regression model, patients with adenomas in the highest versus lowest tertile of dietary calcium intake had 3.4 times higher odds [95% confidence interval (CI), 0.9-12.9] of elevated apoptotic scores. In adenoma-free patients, high calcium intake was not related to apoptosis (OR, 1.2; 95% CI, 0.6-2.7). In contrast, the highest level of 25-hydroxyvitamin D was associated with higher apoptosis in adenoma-free patients (OR, 2.6; 95% CI, 1.1-6.2) and slightly lower levels in patients with adenomas (OR, 0.6; 95% CI, 0.2-2.2).

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium

Miller¹,

Keku

Satia

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Anticarcinogenic effects of calcium in the large bowel have been consistently found in experimental studies (17)(18)(19)(20), and the association of calcium with a reduced risk of colorectal neoplasia is supported by many but not all (21-24), epidemiologic studies (5,6,25,26), and two clinical trials (1,2). It has been hypothesized that calcium protects the colorectal mucosa by binding and precipitating soluble fatty acids and bile acids, preventing irritation and inflammation of the mucosa (20,(27)(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

“…It has been hypothesized that calcium protects the colorectal mucosa by binding and precipitating soluble fatty acids and bile acids, preventing irritation and inflammation of the mucosa (20,(27)(28)(29)(30)(31)(32). Recent studies also suggest a direct effect of extracellular calcium on cellular proliferation and differentiation through the calcium sensing receptor (18,28,(33)(34)(35). The anticarcinogenic properties of NSAIDs in the colorectum are well documented by experimental studies (36)(37)(38)(39)(40)(41), epidemiologic investigations (7,8,(42)(43)(44)(45)(46), and randomized trials (11,(47)(48)(49) Inhibition of cyclooxygenase and mechanisms independent of this enzyme seem involved (13,38,(50)(51)(52)(53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

Interaction of Calcium Supplementation and Nonsteroidal Anti-inflammatory Drugs and the Risk of Colorectal Adenomas

Grau¹,

Baron²,

Barry³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Calcium and aspirin have both been found to be chemopreventive against colorectal neoplasia. However, the joint effect of the two agents has not been well investigated. Methods: To explore the separate and joint effects of calcium and aspirin/nonsteroidal anti-inflammatory drugs (NSAID), we used data from two large randomized clinical trials among patients with a recent history of colorectal adenomas. In the Calcium Polyp Prevention Study, 930 eligible subjects were randomized to receive placebo or 1,200 mg of elemental calcium daily for 4 years. In the Aspirin/Folate Polyp Prevention Study, 1,121 eligible subjects were assigned to take placebo, 81 mg of aspirin, or 325 mg of aspirin daily for 3 years. In each study, subjects completed a validated food frequency questionnaire at enrollment and were asked periodically about medications and supplements used. Recurrent adenomas and advanced adenomas were the end points considered. We used generalized linear models to assess the separate and combined effects of aspirin (or NSAIDs) and calcium supplementation (or dietary calcium) and the interactions between these exposures.

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“…Calcium as a ubiquitous second messenger regulates many cellular functions, including cell growth, differentiation and apoptosis (25)(26)(27). In addition, it was shown by several groups, that calcium can slow down cancer cell division, and administration of calcium offers an approach to the primary prevention of intestinal neoplasia and/or therapy of colorectal cancer metastases (28)(29)(30). In this manner, calcium probably contributes to the anti-tumour activity of AMT.…”

Section: Discussionmentioning

confidence: 99%

AMT: Preclinical pharmacology studies

Scheele¹

2009

Int J Oncol

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Abstract. Auron-Misheil-Therapy (AMT) consisting of aqueous camomile extract supplemented with calcium, vitamins, the antihistamine chlorpheniramine and human insulin is under development as anti-cancer treatment. AMT was preclinically investigated in tumour cell lines and tumour xenografts to guide clinical phase I/II studies. AMT was tested against 56 human tumour cell lines, in a clonogenic assay in 98 patient-derived xenografts and in in vivo studies. AMT showed in vitro cytotoxic activity with highest susceptibility in cervical cancer, glioblastoma and colon cancers. In the clonogenic assay, anti-cancer activity of AMT was most active in cervical and uterine tumours, in colon cancer, glioblastoma, leukaemia, melanoma and pancreatic cancer. In vivo, AMT showed slight activity in tumour xenograft models of colon and mammary cancer. It also showed immune stimulatory effects by induction of IL-6-and TNF-· secretion in human PBMCs. The immune stimulatory potential of AMT, together with slight anti-tumour efficacy observed in the present study, indicates a role of AMT in tumour therapy. IntroductionIn the search for novel, effective anti-cancer treatments not only pure compounds, usually with known modes of action are investigated, but also natural products or more complex preparations, whose substantial anti-tumour activity may be demonstrated before the precise mechanism of action is fully understood. As an example for the latter ones, aqueous extracts of the European mistletoe (Viscum album L.) have been widely used for decades as alternative or complementary treatment and adjuvant cancer therapy particularly in Germany, Austria and Switzerland (1-5).Auron-Misheil-Therapy (AMT) is another representative of a more complex formulation. From compassionate use programs among end-stage cancer patients since 1989, preliminary data have provided evidence of benefits in terms of improved quality of life, sometimes together with body weight gain and reduction of pain. AMT is at present under development as an anti-cancer agent in phase II clinical trials.Preclinical research with AMT revealed pronounced anticancer activity in a range of human tumour models, including bladder, brain, colon, lung, breast, melanoma, prostate and cervix, as well as in cells derived from haematological malignancies, including leukaemias and lymphomas. At the same time, the precise mode of action of AMT remains to be determined. The evidence thus far indicates that its action is predominantly cytotoxic (i.e. actively killing cells) rather than cytostatic (inhibiting mitosis), but the anti-tumour activity of AMT is likely to depend on more than one mechanism, because of the number of different constituents.This study summarizes the preclinical research with AMT with focus on its anti-tumour and immune stimulatory properties. Materials and methodsTest compounds. Auron-Misheil-Therapy (AMT) was provided as sterile, ready-to-use solution by Micro Carrier Systems, Neuss and was stored at 4˚C until use. The single components of AMT, aqueous camomi...

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Dietary calcium supplementation increases apoptosis in the distal murine colonic epithelium

Cited by 35 publications

References 40 publications

Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium

Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium

Interaction of Calcium Supplementation and Nonsteroidal Anti-inflammatory Drugs and the Risk of Colorectal Adenomas

AMT: Preclinical pharmacology studies

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