IL-4 induced proliferation in prostate cancer PC3 cells via regulating LDH-A expression / 实用医学杂志

Objective To study the effects of IL-4 in prostate cancer cells glycometabolism and proliferation. Methods We used IL-4 to treat PC3 cells, then tested the changes of LDH-A expression by RT-qPCR, Western Blot, CCK-8 and lactate production assay. Results Our data showed that IL-4 induced LDH-A up-expression in PC3 cells at mRNA and protein levels. Also, IL-4 promoted the proliferation activation and increased lactate production in PC3 cells. Conclusion IL-4 can strengthen the proliferation activation in PC3 cells by up-regulating LDH-A expression.

High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors.

Aims: Lactate dehydrogenase (LDH)-A is highly expressed in diverse human malignant tumors, parallel to aggressive metastatic disease, resistance to radiation /chemotherapy and clinically poor outcome. Although this enzyme constitutes a plausible target in treatment of advanced cancer, there are few known LDH-A inhibitors. Study Design: In this work, we utilized a high-throughput enzyme micro-array format to screen and evaluate > 900 commonly used medicinal plant extracts (0.00001-.5 mg/ml) for capacity to inhibit activity of recombinant full length human LDHA; EC .1.1.1.27. Methodology: The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI-TOF-MS/MS, enzyme activity was validated by oxidation of NADH (500μM) and kinetic inhibition established in the presence of a known inhibitor (Oxalic Acid). Results: Of the natural extracts tested, the lowest IC50s [<0.001 mg/ml] were obtained by: Chinese Gallnut (Melaphis chinensis gallnut), Bladderwrack (Fucus vesiculosus), Kelp (Laminaria Japonica) and Babul (Acacia Arabica). Forty-six additional herbs contained significant LDH-A inhibitory properties with IC50s [<0.07 mg/ml], some of which have common names of Arjun, Pipsissewa, Cinnamon, Pink Rose Buds/ Petals, Wintergreen, Cat’s Claw, Witch Hazel Root and Rhodiola Root. Conclusion: These findings reflect relative potency by rank of commonly used herbs and plants that contain human LDH-A inhibitory properties. Future research will be required to isolate chemical constituents within these plants responsible for LDH-A inhibition and investigate potential therapeutic application.

Anoxia- and hypoxia-induced expression of LDH-A* in the Amazon Oscar, Astronotus crassipinis

Adaptation or acclimation to hypoxia occurs via the modulation of physiologically relevant genes, such as erythropoietin, transferrin, vascular endothelial growth factor, phosphofructokinase and lactate dehydrogenase A. In the present study, we have cloned, sequenced and examined the modulation of the LDH-A gene after an Amazonian fish species, Astronotus crassipinis (the Oscar), was exposed to hypoxia and anoxia. In earlier studies, we have discovered that adults of this species are extremely tolerant to hypoxia and anoxia, while the juveniles are less tolerant. Exposure of juveniles to acute hypoxia and anoxia resulted in increased LDH-A gene expression in skeletal and cardiac muscles. When exposed to graded hypoxia juveniles show decreased LDH-A expression. In adults, the levels of LDH-A mRNA did not increase in hypoxic or anoxic conditions. Our results demonstrate that, when given time for acclimation, fish at different life-stages are able to respond differently to survive hypoxic episodes.