Antimetabolites have proven successful as therapeutics for advanced-stage breast cancers, but are often accompanied by severe side effects that can limit treatment regimens. 5-Fluorouracil (5-FU), an antimetabolite that inhibits cell proliferation, has served an important role in standard chemotherapy protocols for a variety of solid tumors. Although reasonable response rates have been reported for 5-FU, continued exploration is necessary to improve clinical outcomes and reduce cytotoxic side effects that are an inherent problem for chemotherapeutic interventions. Because of its diverse anticancer properties, we explored whether by combining the natural product curcumin with 5-FU, synergistic improvements in preventing breast cancer cell proliferation and/or provide protection against 5-FU-induced cytotoxicity could be achieved. Indeed both curcumin and 5-FU inhibit DNA synthesis in MDA-MB-231 cells using BrdU incorporation assays; however, combined treatment showed no synergistic improvement. We next established the cytotoxicity profile for 5-FU in MDA-MB-231 cells using a tetrazolium-based cell viability assay and obtained an LD50 value of 28 μM. When 5-FU incubations were repeated with the addition of curcumin, the LD50 value increased to 200-300 μM, representing a 7-10-fold protection by curcumin against 5-FU cytotoxicity. These findings suggest that the addition of curcumin as an adjuvant therapy during 5-FU treatment might enhance the chemotherapeutic effectiveness of 5-FU by protecting normal cells from reduced viability and thus permitting higher dosing or longer treatment times. This would be especially important to those individuals who are plagued with severe cytotoxicities and require frequent interruptions, or even early termination of their treatment regimens.

Haemodialysis (HD) patients have many biochemical, immune and inflammatory alterations that can lead to an increased risk for cardiovascular disease. The two major factors affecting these disorders are (a) metabolic, biochemical, immune or inflammatory alterations due to the uremic syndrome per se and (b) alterations due to the therapeutic treatments of uremia, especially HD-induced stress. HD-induced stress includes activation of the pro-inflammatory transcription factor NF-kB. In the present study, we have employed lipopolysaccharide (LPS) to activate the peripheral blood mononuclear cells (PBMC), as a model of HDinduced stress. The natural products curcumin, resveratrol and parthenolide are known inhibitors of the activation of NF-kB. PBMCs were treated with various concentrations of curcumin, resveratrol and parthenolide and tested for the abilities of these natural products to protect against the LPSinduced expression, secretion of the pro-inflammatory cytokines TNF, IL-1 and IL-6 and activation of the pro-inflammatory COX-2. We report here that parthenolide is an especially effective natural product that limits the development of a pro-inflammatory state by preventing the activation of all four of these pro-inflammatory signals. The approach of limiting the development of a pro-inflammatory state in HD patients during the dialysis procedure by addition of a natural product that protects against activation of NF-kB might be a clinically useful approach to protect leukocytes from HD-induced stress.

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Various chemoattractants have been implicated in the aetiology of the polymorphonuclear leucocyte (PMN) migration into the epidermis seen in early lesions of psoriasis. Using an underagarose technique, the in vitro chemotactic responses of PMN to the arachidonic acid lipoxygenase product leukotriene B₄ (LTB₄) were assayed in five groups of subjects: normal healthy volunteers (n = 12), untreated psoriatics (n = 11) and psoriatics treated with topical tar (n = 12), PUVA (n = 11) and UVB phototherapy (n = 10). No significant difference was observed between the responses of control subjects and of untreated psoriatics, nor between the untreated psoriatic group and the PUVA- and UVB-treated groups, respectively. However, comparison of the tar-treated and untreated groups revealed a significantly increased chemotactic response to LTB₄ in the tar-treated group (p < 0.01).

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