Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 13, Issue 1, 2013

Vitamin D deficiency is a re-emerging global health problem, which is primarily due to inadequate vitamin D synthesis in the skin. Supplement use is an effective measure to improve vitamin D status. However, some safety issues have to be considered, which are highlighted in this review article: The concept of vitamin D safety consists of two models, the safe tolerable upper intake level (UL) method, and the idea of adequate circ Read More

Garland and Garland first hypothesized that better vitamin D status lowered risk of colorectal cancer in 1980. Subsequently, the relation between vitamin D status and colorectal cancer risk has been investigated in epidemiologic studies. Various approaches have been used to estimate vitamin D status, including direct measures of circulating 25(OH)vitamin D levels, surrogates or determinants of vitamin D (including region of re Read More

Vitamin D deficiency and low calcium intake are considered risk factors for several cancers. Vitamin D, synthesized in the skin or ingested through the diet, is transformed through two hydroxylation steps to the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25-D3). 25-hydroxylases in the liver are responsible for the first hydroxylation step. The ultimate activation is performed by the renal 25-hydroxyvitamin D 1α-hydroxylase ( Read More

There is a growing interest for vitamin D in the medical and scientific community as well as in the public medias as illustrated by a huge number of publications. Most experts claim that vitamin D deficiency/insufficiency is widespread with potential important public health consequences. It may seem surprising for many persons that a deficiency in a vitamin may be so frequent in countries where food is so diversified and easily a Read More

The hypothesis that vitamin D deficiency increases the risk of clinical prostate cancer has stimulated an extensive body of research. Ecologic studies have shown that mortality rates from prostate cancer are inversely correlated with levels of ultraviolet radiation, the principal source of vitamin D. Human prostate cells express receptors for 1,25-Dihydroxyvitamin D which exerts pleitropic anticancer effects on these cells i Read More

Cancer patients with advanced disease frequently feel weak and fatigued, and have an increased risk of fracture. At the same time several reports describe the high prevalence of vitamin D deficiency in these patients. This review will summarize the impact of vitamin D deficiency on muscle weakness and fracture risk. While larger clinical trials of vitamin D supplementation are lacking in cancer patients, the evidence from cli Read More

Cancer is a broad term for many disparate diseases with different etiologies, commonly classified by affected organ site. This review summarizes the published evidence from prospective cohort studies examining the associations between vitamin D, measured as serum 25-hydroxyvitamin D (25OHD) concentrations, and the risk of rarer cancer sites including pancreatic, non-Hodgkin lymphoma, ovarian, endometrial, kidney, g Read More

It has been more than 100 years when it was first appreciated that increased sun exposure reduced risk of dying of cancer. The most beneficial effect of sun exposure is the production of vitamin D in the skin. Recent evidence suggests that most cells in the body not only have a vitamin D receptor but also have the capacity to convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Once formed 1,25-dihydroxyvitamin D c Read More

Today, there is a controversial debate in many scientific and public communities on how much sunlight is appropriate to balance between the positive and negative effects of solar UV-exposure. UV exposure undoubtedly causes DNA damage of skin cells and is a major environmental risk factor for all types of skin cancers. In geographic terms, living in parts of the world with increased erythemal UV or high average annual Read More

Based on preclinical studies and early clinical observations, an association between vitamin D status and breast cancer incidence and outcome has been proposed. Against this background, information on vitamin D and breast cancer was reviewed with focused attention on emerging clinical studies in this area. Prospective cohort studies do not associate 25-hydroxyvitamin D levels with breast cancer incidence. While case-co Read More

Accumulating evidence from experimental and epidemiological studies suggests that vitamin D deficiency might be a causal risk factor for cancer and therewith associated mortality. We performed a systematic review in Medline up to February 2012 to identify prospective studies on 25-hydroxyvitamin D (25[OH]D) and cancer mortality as well as on 25(OH)D and survival in cancer patients. Our search retrieved 13 studies Read More

Data from experimental studies suggest that vitamin D receptor activation exerts anti-cancer effects on virtually all steps of carcinogenesis. Epidemiological data support an inverse association of vitamin D serum levels and vitamin D receptor polymorphisms with cancer incidence and mortality. Based on this promising rationale for use of vitamin D and its analogues in cancer prevention and treatment, several intervent Read More

Vitamin D3 is biologically inert. To become active, it requires two successive hydroxylation steps catalyzed by two cytochrome P450 enzymes, first to synthesize the pro-hormone 25-hydroxyvitamin D3 [25(OH)D3] and then the active hormone 1α,25- dihydroxyvitamin D3 [1α,25(OH)2D3]. 1α,25(OH)2D3 has high affinity for the vitamin D receptor (VDR), a transcription factor and a member of the steroid receptor superfamil Read More

The ultraviolet-B (UVB)–vitamin D–cancer hypothesis was proposed in 1980 yet has not been fully accepted. Ecological studies based on geographical variations of cancer rates with respect to solar UVB doses have supported the hypothesis for about 20 cancers. This paper reviews the evidence from studies of personal or group UVB irradiance. Studies have associated personal UVB irradiance with reduced risk for b Read More

Drugs that target microtubules are a successful class of anti-cancer agents that have been in clinical use for over two decades. Acquired resistance to these drugs, however, remains a serious problem. Microtubule alterations, such as tubulin mutations and altered β- tubulin isotype expression, are prominent factors in development of resistance. Changes in actin and intermediate filament proteins can also mediate sensitivity to Read More

Multidrug resistance (MDR) of cancer tissue is a phenomenon in which cancer cells exhibit reduced sensitivity to a large group of unrelated drugs with different mechanisms of pharmacological activity. Mechanisms that reduce cell sensitivity to damage induced by a variety of chemicals were found to be caused by diverse, albeit well-defined, phenotypic alterations. The molecular basis of MDR commonly involves overexpressio Read More

The potential role of carbon nanotubes (CNTs) in the diagnosis and treatment of malignant melanoma (MM) is still an emerging area of research. To date, there is strong evidence for the efficiency of CNTs in this therapeutic area, despite their unique physical, mechanical and biological properties. In this review, the application of CNTs in cancer diagnostics and treatment is reviewed, and consideration is given to the toxicity issues a Read More

Azidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-κB pathway. As multiple myeloma (MM) presents with constitutive activation of NF-κB, we analyzed the effect of AZT on human MM cell lines. We evaluated the cytotoxic effect of AZT in human MM cell lines sensitive (8226/S) or resistant to doxorubicin (8226/DX5) and human T cell lymphoblast-like cells, uterine sarcoma cells, and HU Read More