Cancer statins

Additional agents, including selenium, folic acid, and HMG-CoA reductase inhibitors (statins), show promise as chemopreventive agents in colon cancer, and preliminary and confirmatory studies evaluating their effectiveness have been completed or are ongoing, although none of these agents have been approved for the prevention of colon cancer.46... 

Other agents, including selenium, vitamin E, lycopene, green tea, nonsteriodal anti-inflammatory agents, isoflavones, and statins, are under investigsation for prostate cancer and show promise. Selenium is a naturally occurring trace element that is an essential nutrient in the human diet.8 However, none of these agents is currently recommended for routine use outside a clinical trial. 

Brower V (2003) Of cancer and cholesterol studies elucidate anticancer mechanism of statins. J Natl Cancer Inst 95(12) 844-846... 

Mueck AO, Seeeger H, Wallwiener D (2003) Effect of statins combined with estradiol on proliferation of human receptor-positive and receptor-negative breast cancer cells. Menopause 10(4) 332—336... 

Lipid modifying drugs (statins) have shown secondary cardio-vascular preventive effects (myocardial infarction) in a very large number of patients. Only one study (Shepherd et al. 2002) has been conducted in the elderly and showed similar results. However there was a significant increased cancer risk (25%). 

Dr David Graham from the FDA, speaking to the US senate in 2004, controversially raised concerns (refuted by the respective Pharmaceutical Companies) over the safety of the retinoid, isotretinoin (used in the treatment of cancer), the statin, rosuvastatin (used to lower cholesterol), a long-acting p2-receptor antagonist, salmeterol (used in asthma therapy), and a selective serotonin reuptake inhibitor, paroxetine (used as an antidepressant) (21). 

It has been suspected that low concentrations of serum cholesterol might be associated with an increased risk of cancer or overall mortality. All fibrates and statins cause cancer in rodents, but the relevance of this finding to man has been questioned (68). In an epidemiological study these risks were almost non-existent after adjusting for confounding factors. 

Statin, P., Adlercreutz, H., Tenkanen, L., Jellum, E., Lumme, S., Hallmans, G., Harvei, S., Teppo, L., Stumpf, K., Luostarinew, T., Lehtinen, M., Dillner, M., et al. 2002. Circulating enterolactone and prostate cancer risk A Nordic nested case-control study. Int. J. Cancer 99, 124-129. 

In the five statin megatrials, which collectively randomized over 30,000 patients and had treatment periods of approximately 5 years, new cancers were recorded in over 2000 patients. The numbers of patients with cancer in the active treatment and placebo groups were very similar, as shown in Table III. There was an excess of breast cancer in the pravastatin group in CARE (12 cases vs. 1 in the placebo group), but this is probably an anomalous finding in a small subgroup, as it was not replicable in 4S, LIPID, or AFCAPS, all of which included an appreciable number of female patients (WOS excluded women). The total number of breast cancers in these... 

There has also been considerable interest in the use of statins in other clinical indications, including cancer [75], neurological disorders [76], osteoporosis [77], atrial fibrillation [78], asthma [79], angiogenesis [80], immunomodulatory effects [81], coagulation and thrombosis [82,83]. Whether these effects can all be attributed to the cholesterol-lowering activity or are a consequence of depletion of other isoprenoid species remains to be determined. 

The observation that statins are cytotoxic to a wide variety of cancer cells in vitro coupled with the identification of Ras as an important oncogene, generated much interest in the potential use of statins as... 

PUFAs are potent inhibitors of the HMG-CoA reductase enzyme and similar to statins are useful in the treatment of hyperlipidemias (99-102). Statins enhance plasma AA levels and decrease the ratio of EPA to AA significantly (100). This finding suggests that PUFAs mediate many actions of statins (103) and that this could be one mechanism by which they lower cholesterol levels. Statins and PUFAs have many overlap actions such as the inhibition of IL-6 and TNF-a production and NF-kB activation plus the ability to enhance eNO production thus, both possess anti-inflammatory actions and both are useful in atherosclerosis, coronary heart disease, osteoporosis, stroke, Alzheimer s disease, and inflammatory conditions such as lupus and cancer (3, 4, 94, 104-121). These similar and overlap actions strongly indicate that the molecular mechanisms of actions of statins and PUFAs are similar, if not identical. Furthermore, when a combination of statins and PUFAs are given together, a synergistic beneficial effect was seen in patients with combined hyperlipemia (122). 

Statin has been elaborated. This successful synthesis now opens up new opportunities for the development of new tools for biological studies and new cancer drugs. 

Madhusudan S, Protheroe A, Propper D, Han C, Corrie P, Earl H, Hancock B, Vasey P, Turner A, BalkwiU F, Hoare S, Harris AL. A multicentre phase II trial of bryo-statin-I in patients with advanced renal cancer. Br J Cancer 2003 89(8) 1418-22. 

Graaf MR, Beiderbeck AB, Egberts ACG, et al. The risk of cancer in users of statins. J Clin Oncol 2004 22 2388-2394. 

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