Recent studies have shown that high insulin-like growth factor I (IGF-I) blood level is a risk factor in breast and prostate cancer. The aim of this study was to determine whether the mitogenic activity of IGF-I in mammary cancer cells can be reduced by the dietary carotenoid lycopene. The anticancer activity of lycopene, the major tomato carotenoid, has been suggested by in vitro, in vivo, and epidemiological studies. Growth stimulation of MCF7 mammary cancer cells by IGF-I was markedly reduced by physiological concentrations of lycopene. The inhibitory effects of lycopene on MCF7 cell growth were not accompanied by apoptotic or necrotic cell death, as determined by annexin V binding to plasma membrane and propidium iodide staining of nuclei in unfixed cells. Lycopene treatment markedly reduced the IGF-I stimulation of tyrosine phosphorylation of insulin receptor substrate 1 and binding capacity of the AP-1 transcription complex. These effects were not associated with changes in the number or affinity of IGF-I receptors, but with an increase in membrane-associated IGF-binding proteins, which were previously shown in different cancer cells to negatively regulate IGF-I receptor activation. The inhibitory effect of lycopene on IGF signaling was associated with suppression of IGF-stimulated cell cycle progression of serum-starved, synchronized cells. Moreover, in cells synchronized by mimosine treatment, lycopene delayed cell cycle progression after release from the mimosine block. Collectively, the above data suggest that the inhibitory effects of lycopene on MCF7 cell growth are not due to the toxicity of the carotenoid but, rather, to interference in IGF-I receptor signaling and cell cycle progression.

Lycopene, the major tomato carotenoid, has been found to inhibit proliferation of several types of cancer cells, including those of breast, lung, and endometrium. By extending the work to the HL-60 promyelocytic leukemia cell line, we aimed to evaluate some mechanistic aspects of this effect. Particularly, the possibility was examined that the antiproliferative action of the carotenoid is associated with induction of cell differentiation. Lycopene treatment resulted in a concentration-dependent reduction in HL-60 cell growth as measured by [3H]thymidine incorporation and cell counting. This effect was accompanied by inhibition of cell cycle progression in the G0/G1 phase as measured by flow cytometry. Lycopene alone induced cell differentiation as measured by phorbol ester-dependent reduction of nitro blue tetrazolium and expression of the cell surface antigen CD14. Results of several recent intervention studies with beta-carotene, which have revealed no beneficial effects of this carotenoid, suggest that a single dietary component cannot explain the anticancer effect of diets rich in vegetables and fruits. Thus another goal of our study was to examine whether lycopene has the ability to synergize with other natural anticancer compounds, such as 1,25-dihydroxyvitamin D3, which when used alone are therapeutically active only at high and toxic concentrations. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure.

There is extensive evidence that high intake of fruits and vegetables is associated with decreased risk of many types of cancers. Thus, it is widely accepted that diet changes are a powerful means to prevent cancer. Although there is a growing interest in the role of the tomato carotenoid lycopene in cancer prevention and treatment, we hypothesize that a single micronutrient cannot replace the power of the concerted action of multiple agents derived from a diet rich in fruits and vegetables. Indeed, we found that lycopene can synergize with other phytonutrients in the inhibition of cancer cell growth. The mechanism underlying the inhibitory effects of lycopene and other carotenoids involves interference in several pathways related to cancer cell proliferation and includes changes in the expression of many proteins participating in these processes, such as connexins, cyclins, cyclin-dependent kinases, and their inhibitors. These changes in protein expression suggest that the initial effect involves modulation of transcription by ligand-activated nuclear receptors or by other transcription factors. It is feasible to suggest that carotenoids and their oxidized derivatives interact with a network of transcription systems that are activated by different ligands at low affinity and specificity and that this activation leads to the synergistic inhibition of cell growth.

Chronic ankle instability is a common complication of ankle sprain. The clinical assessment of ankle instability is usually incomplete and difficult to interpret. Recently, more attention has been paid to the value of the anterior drawer test of the ankle. We assessed the accuracy of a modification of the anterior drawer test, comparing it with radiological stress view of the ankle in 25 patients with recurrent ankle sprain. The radiological examinations were performed by a TELOS instrument and included lateral and anteroposterior stress views. We found that the modified anterior drawer test correlated with the posterior opening of the tibiotalar joint and with the lateral tilt of the talus. We conclude that a slightly positive modified anterior drawer test may indicate injury to the anterior talofibular ligament. A significant movement of the ankle elicited by the modified anterior drawer test may indicate combined injury to anterior talofibular and calcaneofibular ligaments.