Crude extract of Rheum palmatum L induced cell death in LS1034 human colon cancer cells acts through the caspase‐dependent and ‐independent pathways

Crude extract of Rheum palmatum L (CERP) has been used to treat different diseases in the Chinese population for decades. In this study, we investigated the effects of CERP on LS1034 human colorectal cancer cells in vitro and also examined possible mechanisms of cell death. Flow cytometric assays were used to measure the percentage of viable cells, cell cycle distribution including the sub‐G1 phase (apoptosis), the activities of caspase‐8, ‐9, and ‐3, reactive oxygen species (ROS) and Ca²⁺ levels, and mitochondrial membrane potential (ΔΨ_m). DNA damage, nuclei condensation, protein expression, and translocation were examined by Comet assay, 4′‐6‐diamidino‐2‐phenylindole (DAPI) staining, Western blotting, and confocal laser system microscope, respectively. CERP induced apoptosis as seen by DNA fragmentation and DAPI staining in a concentration‐ and time‐dependent manner in cancer cells. CERP was associated with an increase in the Bax/Bcl‐2 protein ratio and CERP promoted the activities of caspase‐8, ‐9, and ‐3. Both ROS and Ca²⁺ levels were increased by CERP but the compound decreased levels of ΔΨ_m in LS1034 cells. Laser confocal microscope also confirmed that CERP promoted the expressions of AIF, Endo G, cytochrome c, and GADD153 to induce apoptosis through mitochondrial‐dependent pathway. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 969–980, 2014.     

Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D‐galactose induced aging in rats

Cardiac fibrosis is a common pathophysiological process observed during chronic and stress‐induced acceleration of cardiac aging. Fibrosis is a necessary process during wound healing and tissue repair. However, its deposition in organs would proceed to scarring and organ damage. Here Alpinate Oxyphyllae Fructus (AOF), a Chinese medicine extract was used to protect aging heart from collagen accumulation. About 8 weeks old, male SD rats were randomly divided into (i) Control, (ii) D‐galactose induced aging (IA), (iii) IA + AOF 50 (AOF low, AL), (iv) IA + AOF 100 (AOF medium, AM), (v) IA + AOF 150 (AOF high, AH) mg/kg/day, AOF was administered orally. After 8 weeks rats were sacrificed and hearts were collected. Results showed collagen deposition and up‐regulation of matrix metalloproteinases‐MMP‐2 and ‐9 in D‐galactose‐induced aging rats. Furthermore, western blotting and immunostaining were also confirmed the upregulation of TGF‐β1 mediated fibrosis in aging induced rats. However, collagen deposition and fibrosis were significantly decreased by AOF treatments (AM and AH). AOF treatments salvaged the cardiac fibrosis. Hence, AOF might be a potential therapeutic agent in the prevention of cardiac fibrosis associated with aging. The protective effects of AOF might have promising results in anti‐aging treatments.     

Coronarin D induces human oral cancer cell apoptosis though upregulate JNK1/2 signaling pathway

The incidence of oral cancer is increasing all over the world, with rates particularly high in Southeast Asian countries, such as Taiwan. Coronarin D (CD) has been confirmed to have anti‐inflammatory, anti‐bacterial effects, and anti‐apoptotic effects in human hepatocellular carcinoma and nasopharyngeal carcinoma. The purpose of this study is to explore whether CD has a suppression effect on oral cancer cells and the mechanisms involved. The results of our study revealed the significantly decreased cancer cell viability and increased activation of apoptosis via increased loss of mitochondrial membrane potential, increased death receptors, leading to the activation of caspase‐8, ‐9, ‐3. Moreover, the rate of apoptosis of cells treated with CD plus JNK inhibitors was decreased compared to CD‐treated cells. This is the first study to demonstrate that CD induces apoptosis in human oral cancer cells and can be expected to be a promising anticancer agent for oral cancer treatment.     

Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms

Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti‐inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP‐2 and/or MMP‐9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 μM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 μM naringenin. Zymography analysis also revealed that the activities of MMP‐2 and MMP‐9 of GBM cells were significantly inhibited in response to 100, 200, or 300 μM naringenin treatment. Proteins of MMP‐2 and MMP‐9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.     

Sesame Oil Therapeutically Ameliorates Cardiac Hypertrophy by Regulating Hypokalemia in Hypertensive Rats

Background: Hypokalemia and hypertension are common manifestations of preclinical cardiovascular conditions that have a predictive value for cardiovascular morbidity and mortality. Cardiac hypertrophy, an important risk factor in heart failure, is attributed to long‐term hypokalemia and hypertension. Sesame oil is rich in nutrients and possesses potent antihypertensive activities. Methods: We investigated the therapeutic potential of sesame oil using a hypertensive model created by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/mL/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was administered by oral gavage (0.5 or 1 mL/kg/d for 7 days) after 4 weeks of DOCA/salt treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), electrocardiography (ECG), and K⁺ and Mg²⁺ levels were assessed 24 hours after the last dose of sesame oil. Heart tissue was collected for histologic analysis. Results: Sesame oil effectively reduced the SBP/DBP and ECG abnormalities and increased the serum levels of K⁺ and Mg²⁺ while limiting the urinary excretion of K⁺ in DOCA/salt‐induced hypertensive rats. In addition, sesame oil decreased the heart mass, the thickness of the left ventricle, and the diameter of cardiomyocytes, indicating the regression of left ventricular hypertrophy in the hypertensive rats. Conclusion: We demonstrate that sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.