Corosolic acid enhances oxidative stress-induced apoptosis and senescence in pancreatic cancer cells by inhibiting the JAK2/STAT3 pathway.

BACKGROUND: Pancreatic cancer (PC) is a fatal human malignancy with a poor prognosis. Corosolic acid (CRA) is a triterpenoid, has been reported to have inhibitory effects on tumor growth. However, the role of CRA on PC has not been explored. Here, we aimed to uncover the molecular mechanisms of CRA in PC progression. METHODS: Cell viability, lactate dehydrogenase (LDH) release, cell apoptosis and senescence were detected by cell counting kit-8 (CCK-8), LDH, flow cytometry and senescence associated-ß-galactosidase (SA-ß-gal) assay. Levels of relevant proteins and oxidative stress (OS) markers were evaluated by Western blot and enzyme-linked immunosorbent assay (ELISA). A xenograft tumor model was established to explore the in vivo effects of CRA on PC. RESULTS: We found that CRA inhibited PC cell viability and promoted LDH release in a dose-dependent manner, but had no significant effect on human normal pancreatic ductal epithelial cells HPDE6C7. CRA increased OS-induced cell apoptosis and senescence in HAPC and SW1990 cells. And CRA decreased the levels of anti-apoptotic protein Bcl-2, and elevated the expression of pro-apoptotic protein Bax and senescence-associated proteins P21 and P53. Besides, CRA decreased tumor growth in xenograft models. Furthermore, CRA inactivated the Janus kinase-2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in HAPC and SW1990 cells. Functional experiments demonstrated that activation of the JAK2/STAT3 pathway by the JAK2 activator coumermycin A1 (C-A1) or the STAT3 activator colivelin (col) reduced the contribution effect of OS, apoptosis and senescence by CRA. CONCLUSION: Taken together, our findings indicated that CRA exerted anti-cancer effects in PC by inhibiting the JAK2/STAT3 pathway.

The Berberis vulgaris L. extract berberine exerts its anti-oxidant effects to ameliorate cholesterol overloading-induced cell apoptosis in the primary mice hepatocytes: an in vitro study.

Cholesterol overloading stress damages normal cellular functions in hepatocytes and induces metabolic disorders to facilitate the development of multiple diseases, including cardiovascular diseases, which seriously degrades the life quality of human beings. Recent data suggest that the Berberis vulgaris L. extract berberine is capable of regulating cholesterol homeostasis, which is deemed as potential therapeutic drug for the treatment of cholesterol overloading-associated diseases, but its detailed functions and molecular mechanisms are still largely unknown. In the present study, we evidenced that berberine suppressed cell apoptosis in high-cholesterol-diet mice liver and cholesterol-overloaded mice hepatocytes. Also, cholesterol overloading promoted reactive oxygen species (ROS) generation to trigger oxidative damages in hepatocytes, which were reversed by co-treating cells with both berberine and the ROS scavenger N-acetylcysteine (NAC). Moreover, the underlying mechanisms were uncovered, and we validated that berberine downregulated Keap1, and upregulated Nrf2 to activate the anti-oxidant Nrf2/HO-1 signaling pathway in cholesterol overloading-treated hepatocytes, and both Keap1 upregulation and Nrf2 downregulation abrogated the suppressing effects of berberine on cell apoptosis in the hepatocytes with cholesterol exposure. Taken together, we concluded that berberine activated the anti-oxidant Keap1/Nrf2/HO-1 pathway to eliminate cholesterol overloading-induced oxidative stress and apoptotic cell death in mice hepatocytes, and those evidences hinted that berberine might be used as putative therapeutic drug for the treatment of cholesterol overloading-associated cardiovascular diseases.

Age, gender and metabolic syndrome-related coronary heart disease in U.S. adults.

BACKGROUND: Metabolic syndrome (MetS), a clustering of several prominent risk factors for atherosclerosis, is common among U.S. populations. The contribution of MetS to the prevalence of coronary heart disease (CHD) in different age-gender groups is currently unknown. METHODS: MetS was defined according to the definition of the National Cholesterol Education Program Adult Treatment Panel III. CHD was defined as having had a diagnosed heart attack in self-reported medical history. Data from the Third National Health and Nutrition Examination Survey (NHANES III) were used to evaluate the MetS-associated CHD prevalences in different age-gender subpopulations, which include 35- to 54-year-old women, 55- to 74-year-old women, 35- to 54-year-old men, and 55- to 74-year-old men. RESULTS: The prevalences of MetS in these 4 age-gender subpopulations are 21%, 24%, 39%, and 38%, respectively. The odds ratios (and the 95% confidence intervals) of MetS to increased CHD in each subpopulations are 1.05 (0.40-2.79), 1.95 (1.19-3.20), 2.22 (1.03-4.81), and 1.96 (1.41-2.70), respectively. CONCLUSIONS: MetS-associated CHD prevalence in women aged 35-54 years is almost the same as in the control, whereas in women aged 55-74 and in men aged 35-54 or 55-74, this prevalence is about 2-fold that of the control. Endogenous estrogen may play a role in suppressing the pro-atherosclerotic effects of MetS-related risk factors, but further studies are needed for a more certain conclusion.

Relation of coronary artery calcium to left ventricular mass in African-Americans.

Both coronary artery calcium (CAC) deposits and increased left ventricular (LV) mass are important risk factors for coronary heart disease, but the relation between these 2 factors has rarely been studied. We examined the correlation of CAC and LV mass in 159 young to middle-aged African-Americans, and found that the average LV mass indexes were bigger in the CAC-positive groups than in CAC-negative groups in both genders (p = 0.0004 in men; p = 0.08 in women).