Chemical screening identifies the anticancer properties of Polyporous parvovarius.

One of the biggest obstacles in cancer treatment is the development of chemoresistance. To overcome this, attempts have been made to screen novel anticancer substances derived from natural products. The purpose of this study is to find new anticancer candidates in the mycelium culture extract of mushrooms belonging to Polyporus. Here, we used a high-throughput screening to find agents capable of inhibiting cancer cell proliferation. The culture extract of Polyporus Parvovarius mycelium in DY medium (pp-DY) was effective. pp-DY inhibited cancer cell proliferation by inducing apoptosis and S-phase arrest. The anticancer property of pp-DY was not only effective against one type of cancer, but also against another type of cancer. Compound fractionation was performed, and the active ingredient exhibiting anticancer effects in pp-DY was identified as 3,4-dihydroxybenzaldehyde (Protocatechualdehyde, PCA). PCA, like pp-DY, inhibited the proliferation of cancer cells by inducing apoptosis and S-phase arrest. Furthermore, unlike conventional anticancer drugs, PCA did not increase the proportion of the side population that plays the most important role in the development of chemoresistance. Taken together, our data revealed the novel mycelium culture extract that exhibited anticancer property, and identified active ingredients that did not activate a proportion of the side population. These novel findings may have clinical applications in the treatment of cancer, particularly chemo-resistant cancer.

Restoration of Lysosomal and Mitochondrial Function Through p38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Senescence.

Oncogene-induced senescence (OIS), characterized by irreversible cell cycle arrest by oncogene activation, plays an important role in the pathogenesis of aging and age-related diseases. Recent research indicates that OIS is driven by activation of mitogen-activated protein kinase (MAPK). However, it is not apparent whether MAPK inhibition helps to recover senescence. In our previous study, we uncovered p38 MAPK inhibitor, SB203580, as an effective agent to reduce reactive oxygen species and increase proliferation in premature senescent cells. In this study, we evaluated whether SB203580 could ameliorate senescence in normal senescent cells. The senescence-improving effect was observed in the results that SB203580 treatment restored lysosomal function, as evidenced by a decrease in lysosomal mass and an increase in autophagic vacuoles. Then, SB203580-mediated lysosomal function restoration triggered the clearance of damaged mitochondria, leading to metabolic reprogramming necessary for amelioration of senescence. Indeed, p38 MAPK inhibition by SB203580 improved key senescent phenotypes. Our findings suggest a novel mechanism by which modulation of p38 MAPK activity leads to senescence improvement through functional restoration of lysosome and mitochondria.

Metabolic reprogramming as a novel therapeutic target for Coxsackievirus B3.

Coxsackievirus B3 (CVB3) is a single-stranded RNA virus that belongs to the Enterovirus genus. CVB3 is a human pathogen associated with serious conditions such as myocarditis, dilated cardiomyopathy, and pancreatitis. However, there are no therapeutic interventions to treat CVB3 infections. In this study, we found that CVB3 induced metabolic alteration in host cells through increasing glycolysis level, as indicated by an increase in the extracellular acidification rate (ECAR). CVB3-mediated metabolic alteration was confirmed by metabolite change analysis using gas chromatography-mass spectrometry (GC-MS). Based on findings, a strategy to inhibit glycolysis has been proposed to treat CVB3 infection. Indeed, glycolysis inhibitors (2-Deoxy-D-glucose, sodium oxide) significantly reduced CVB3 titers after CVB3 infection, indicating that glycolysis inhibitors can be used as effective antiviral agents. Taken together, our results reveal a novel mechanism by which CVB3 infection is controlled by regulation of host cell metabolism.