ABSTRACT
OBJECTIVE: Celastrol, a triterpene from the root bark of the Chinese medicinal plant Tripterygium wilfordii, has been shown to exhibit anti-oxidant, anti-inflammatory, anti-cancer and insecticidal activities. Also, it has been demonstrated that celastrol has obesity-controlling effects in diet-induced obesity mice. However, direct evidence that celastrol contributes to the development of adipocyte differentiation and lipolysis has not been fully elucidated. Moreover, no previous studies have evaluated whether celastrol may regulate adipogenic transcriptional markers in adipocytes. MATERIALS/METHODS: In order to address the questions above, we extended previous observations and investigated in vitro celastrol signaling study whether celastrol may regulate differentiation, lipolysis and key adipogenic transcriptional pathways in 3T3-L1 adipocytes. RESULTS: Treatment of celastrol not only inhibited adipocyte differentiation (lipid accumulation, glyceraldehyde-3-phosphate dehydrogenase activity and triglyceride content) but also increased lipolysis (glycerol release and free fatty acid release) in 3T3-L1 adipocytes. In addition, all celastrol-regulated functional activities were controlled by PPARγ(2) and C/EBPα signaling pathways in duration of celastrol's treatment in 3T3-L1 adipocytes. CONCLUSION: Our initial data from in vitro celastrol signaling studies suggest novel insights into the role of PPARγ(2) and C/EBPα as probable mediators of the action of celastrol in regulating adipocyte differentiation and lipolysis in 3T3-L1 adipocytes.
Subject(s)
Adipocytes, White/drug effects , Adipogenesis/drug effects , Anti-Obesity Agents/pharmacology , CCAAT-Enhancer-Binding Protein-alpha/antagonists & inhibitors , Lipolysis/drug effects , PPAR gamma/antagonists & inhibitors , Triterpenes/pharmacology , 3T3-L1 Cells , Adipocytes, White/cytology , Adipocytes, White/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Obesity Agents/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/adverse effects , Antioxidants/pharmacology , Biomarkers/chemistry , Biomarkers/metabolism , CCAAT-Enhancer-Binding Protein-alpha/genetics , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Cell Survival/drug effects , Gene Expression Regulation/drug effects , Insecticides/toxicity , Kinetics , Mice , PPAR gamma/genetics , PPAR gamma/metabolism , Pentacyclic Triterpenes , RNA, Messenger/metabolism , Signal Transduction/drug effects , Triterpenes/adverse effectsABSTRACT
We utilized subcutaneous (SC)- and omental (OM)-derived human primary adipocytes (hPA) from obese male, and investigated whether synthetic analog of leptin, metreleptin, may regulate lipolysis via translocation of STAT3 to the nucleus. We observed that 50 ng/mL of metreleptin increases STAT3 phosphorylation in both SC- and OM-derived hPA. Importantly, we found for the first time that metreleptin is capable of trans-locating STAT3 to the nucleus and STAT3 blockade inhibits metreleptin-induced lipolysis. Our initial data provide novel insights into the role of STAT3 as probable mediator of the action of metreleptin in regulating metabolism.
ABSTRACT
α-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate cancer cells. However, direct evidence that ALA contributes to the development of colon cancer has not been fully elucidated. In addition, no previous studies have evaluated whether ALA may regulate malignant potential, such as adhesion, invasion, and colony formation of colon cancer cells. To address the aforementioned questions, we conducted in vitro ALA signaling studies using human (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell proliferation is reduced by ALA administration in a dose-dependent manner in human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration of ALA significantly decreased cell proliferation when compared with control. Similarly, we found that ALA downregulates adhesion, invasion, and colony formation. Finally, we observed that ALA activates p53 and AMPK signaling pathways in human and mouse colon cancer cells. We found for the first time that ALA suppresses cell proliferation and malignant potential via p53 and AMPK signaling pathways in human and mouse colon cancer cells. These new and early mechanistic studies provide a causal role of ALA in colon cancer, suggesting that ALA might be a useful agent in the management or chemoprevention of colon cancer.
