1.
Regulation of Autophagy in Cardiovascular Diseases by Natural Products.
Gu, S, Li, X
Advances in experimental medicine and biology. 2020;:731-736
Abstract
Several major cardiovascular diseases, such as heart failure (HF) and atherosclerosis (AS), have been linked to autophagy dysfunction. The influence of autophagy on the occurrence and development of cardiovascular diseases has two sides. Generally, the induction of autophagy at a low level can provide energy and nutrients for cells through degradation of damaged organelles, protect cardiomyocytes and vascular endothelial cells, and stabilize atherosclerotic plaques. However, excessive autophagy may damage cardiomyocytes and vascular endothelial cells and even cause cell death. Therefore, the study on the role and mechanism of autophagy in the pathogenesis of cardiovascular diseases may not only provide new targets for the treatment of cardiac remodeling, myocardial ischemia and reperfusion injury, atherosclerosis and heart failure, but also provide clues for the developing new drugs on prevention and treatment of clinical cardiovascular diseases. In this chapter, we reviewed the research progress on resveratrol, curcumin, epigallocatechin-3-gallate, and cordyceps sinensis on their recent research progress for cardiovascular diseases. Regulating autophagy may be an effective strategy for the treatment of cardiovascular diseases in the future.
2.
Regulation of Autophagy in Neurodegenerative Diseases by Natural Products.
Liu, S, Li, X
Advances in experimental medicine and biology. 2020;:725-730
Abstract
Neurodegenerative diseases mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD). It is now found that these diseases may be related to autophagic dysfunction. The mechanism is due to abnormalities in autophagy, which lead to abnormal or misfolded proteins accumulating in the cytoplasm, nucleus, and extracellular inclusion bodies, causing neuronal organelle damage and synaptic dysfunction. Since these diseases are much complex, the effect of monotherapy is not significantly affected. There is still a need to strengthen the study of anti-neurodegenerative drugs. Natural products should be a good source for the new drug discovery since most of natural products are multiple-target compounds. In this chapter, we reviewed some progress on studying resveratrol, curcumin, tripterine, and paeoniflorin. These natural products can eliminate abnormal protein aggregates by regulating autophagy, and thereby these compounds are promising to be used in prevention and treatment of neurodegenerative diseases in the future.
3.
Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy.
Hong, F, Gao, Y, Li, Y, Zheng, L, Xu, F, Li, X
World journal of surgical oncology. 2020;(1):113
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms. METHODS The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. RESULTS HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. CONCLUSIONS HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.
4.
Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells.
Li, X, Li, X, Wang, J, Ye, Z, Li, JC
International journal of biological sciences. 2012;(6):901-12
Abstract
BACKGROUND Oridonin (ORI) could inhibit the proliferation and induce apoptosis in various cancer cell lines. However, the mechanism is not fully understood. METHODS Human prostate cancer (HPC) cells were cultured in vitro and cell viability was detected by the CCK-8 assay. The ultrastructure changes were observed under transmission electron microscope (TEM). Chemical staining with acridine orange (AO), MDC or DAPI was used to detect acidic vesicular organelles (AVOs) and alternation of DNA. Expression of LC3 and P21 was detected by Western Blot. Apoptotic rates and cell cycle arrest were detected by FACS. RESULTS Our study demonstrated that after ORI treatment, the proliferations of human prostate cancer (HPC) cell lines PC-3 and LNCaP were inhibited in a concentration and time-dependent manner. ORI induced cell cycle arrest at the G2/M phase. A large number of autophagosomes with double-membrane structure and acidic vesicular organelles (AVOs) were detected in the cytoplasm of HPC cells treated with ORI for 24 hours. ORI resulted in the conversion of LC3-I to LC3-II and recruitment of LC3-II to the autophagosomal membranes. Autophagy inhibitor 3-methyladenine (3-MA) reduced AVOs formation and inhibited LC3-I to LC3-II conversion. At 48 h, DNA fragmentation, chromatin condensation and disappearance of surface microvilli were detected in ORI-treated cells. ORI induced a significant increase in the number of apoptotic cells (PC-3: 5.4% to 27.0%, LNCaP: 5.3% to 31.0%). Promoting autophagy by nutrient starvation increased cell viability, while inhibition of autophagy by 3-MA promoted cell death. The expression of P21 was increased by ORI, which could be completely reversed by the inhibition of autophagy. CONCLUSIONS Our findings indicated that autophagy occurred before the onset of apoptosis and protected cancer cells in ORI-treated HPC cells. P21 was involved in ORI-induced autophagy and apoptosis. Our results provide an experimental basis for understand the anti-tumor mechanism of ORI as treatment for prostate cancer.