Lactate is an important metabolite in cellular metabolism and fluctuates in certain disease conditions including cancer and immune diseases. It was hypothesized that a decrease in lactate would modulate the inflammatory response elicited by lipopolysaccharides (LPS) in macrophages. When RAW 264.7 macrophages were treated with FX11, a specific lactate dehydrogenase (LDHA) inhibitor, the expression of the cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) was downregulated due to reduced cellular lactate levels. Genetic suppression of LDHA by small interfering RNA (siRNA) downregulated the LPS-activated expression of interleukin (IL)-6, iNOS, and COX-2, and reduced the production of IL-6 and nitrites. Pharmacological and genetic suppression of LDHA inhibited the phosphorylation of p38 mitogen-activated protein kinase. Microarray gene expression profile demonstrated that the genes involved in cell proliferation and inflammation were mainly altered by siRNA-mediated LDHA suppression. Collectively, the present observations suggest that lactate may be an important metabolite and implicated in regulation of inflammatory response.

Pancreatic cancer, the seventh most lethal cancer around the world, is considered complicated cancer due to poor prognosis and difficulty in treatment. Despite all the conventional treatments, including surgical therapy and chemotherapy, the mortality rate is still high. Therefore, the possibility of using natural products for pancreatic cancer is increasing. In this study, 68 natural products that have anti-pancreatic cancer effects reported within five years were reviewed. The mechanisms of anti-cancer effects were divided into four types: apoptosis, anti-metastasis, anti-angiogenesis, and anti-resistance. Most of the studies were conducted for natural products that induce apoptosis in pancreatic cancer. Among them, plant extracts such as Eucalyptus microcorys account for the major portion. Some natural products, including Moringa, Coix seed, etc., showed multi-functional properties. Natural products could be beneficial candidates for treating pancreatic cancer.

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