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We reported previously that jasmonates can kill human cancer cells.

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Background and purpose: No current treatment reliably affects the course of metastatic melanoma. Consequently, novel approaches to the control of metastasis are actively sought. The overall goal of the present study was to identify new antimetastatic agents active against melanoma cells. Experimental approach: Two directions were taken: 1. To determine whether the natural plant hormone methyl jasmonate, which kills cancer cells selectively, can suppress the characteristic metastatic behavior of B16-F10 melanoma cells; 2. To synthesize and identify novel jasmonate derivatives with better cytotoxic and anti-metastatic activities than methyl jasmonate. Key results: We found that methyl jasmonate suppressed B16-F10 cell motility and inhibited the development of experimental lung metastases of these cells. Furthermore, methyl jasmonate suppressed the motility of a sub-clone of these cells overexpressing P-glycoprotein and exhibiting multidrug resistance. The synthetic derivative Compound I (5,7,9,10-tetrabromo derivative of methyl jasmonate, the most active derivative) had greater cytotoxic potency (IC 50 , 0.04mM) than methyl jasmonate (IC 50 , 2.6mM). Compound I prevented B16-F10 cell adhesion efficiently and inhibited the development of lung metastases at a much lower dose than methyl jasmonate. Conclusions and Implications: Natural and synthetic jasmonates have anti-metastatic actions. Further development of these agents for the suppression of metastasis in melanoma and other types of cancer is warranted.

BackgroundPlasmodium and Schistosoma are two of the most common parasites in sub-tropical areas. Deregulation of the immune response to Plasmodium falciparum, characterized by a Th1 response, leads to cerebral malaria (CM), while a Th2 response accompanies chronic schistosomiasis.MethodsThe development of CM was examined in mice with concomitant Schistosoma mansoni and Plasmodium berghei ANKA infections. The effect of S. mansoni egg antigen injection on disease development and survival was also determined. Cytokine serum levels were estimated using ELISA. Statistical analysis was performed using t-test.ResultsThe results demonstrate that concomitant S. mansoni and P. berghei ANKA infection leads to a reduction in CM. This effect is dependent on infection schedule and infecting cercariae number, and is correlated with a Th2 response. Schistosomal egg antigen injection delays the death of Plasmodium-infected mice, indicating immune involvement.ConclusionsThis research supports previous claims of a protective effect of helminth infection on CM development. The presence of multiple parasitic infections in patients from endemic areas should therefore be carefully noted in clinical trials, and in the development of standard treatment protocols for malaria. Defined helminth antigens may be considered for alleviation of immunopathological symptoms.