No abstract

Zanthoxylum fruit, obtained from the Japanese pepper plant (Zanthoxylum piperitum De Candolle), and its extract (Zanthoxylum fruit extract, ZFE) have multiple physiological activities (e.g., antiviral activity). However, the potential anticancer activity of ZFE has not been fully examined. In this study, we investigated the ability of ZFE to induce autophagic cell death (ACD). ZFE caused remarkable autophagy-like cytoplasmic vacuolization, inhibited cell proliferation, and ultimately induced cell death in the human cancer cell lines DLD-1, HepG2, and Caco-2, but not in A549, MCF-7, or WiDr cells. ZFE increased the level of LC3-II protein, a marker of autophagy. Knockdown of ATG5 using siRNA inhibited ZFE-induced cytoplasmic vacuolization and cell death. Moreover, in cancer cells that could be induced to undergo cell death by ZFE, the extract increased the phosphorylation of c-Jun N-terminal kinase (JNK), and the JNK inhibitor SP600125 attenuated both vacuolization and cell death. Based on morphology and expression of marker proteins, ZFE-induced cell death was neither apoptosis nor necrosis. Normal intestinal cells were not affected by ZFE. Taken together, our findings show that ZFE induces JNK-dependent ACD, which appears to be the main mechanism underlying its anticancer activity, suggesting a promising starting point for anticancer drug development.

Background/Aims: SM22α, transgelin, is abundantly expressed in smooth muscle tissues and our previous work demonstrated that it is a novel marker of injured glomerular epithelial cells in rat antiglomerular basement membrane nephritis. In this study, we investigated SM22α expression in models of glomerular and interstitial renal injury. Methods: The 5/6 nephrectomy (Nx) model, ischemia-reperfusion (I/R) model and puromycin aminonucleoside (PAN) nephrosis of rats were studied. Immunohistochemical analyses and immunoelectron microscopic studies of SM22α expression were performed. Results: In the 5/6 Nx model, SM22α was first expressed in peritubular interstitial cells and was also expressed in injured glomerular epithelial cells at 8 weeks. In the I/R model, SM22α expression was induced in peritubular interstitial cells as early as 12 h after I/R with expression sustained at 7 days. However, SM22α was not detected in any glomerular cells or tubular epithelial cells. In PAN nephrosis, SM22α was only expressed in glomerular epithelial cells after 1 week, but expression was transient. Conclusion: SM22α was expressed in glomerular epithelial cells and interstitial cells in renal injury. SM22α is differentially upregulated in various models of renal injury and merits further study.

SM22α was expressed in epithelial cells of inflamed glomeruli in the early phase, and then also in peritubular interstitial cells in the later phase of anti-GBM nephritis model. SM22α presented unique kinetics of expression distinct from αSMA.