EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: Role of ROS accumulation, caspase-8 activation, and autophagy induction

2012 ◽  
Vol 114 (1) ◽  
pp. 192-203 ◽  
Author(s):  
Masayuki Fukui ◽  
Ki Sung Kang ◽  
Kazushi Okada ◽  
Bao Ting Zhu
Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 570
Author(s):  
Hajar Dahou ◽  
Marie-Albane Minati ◽  
Patrick Jacquemin ◽  
Mohamad Assi

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with few therapeutic options. The identification of new promising targets is, therefore, an urgent need. Using available transcriptomic datasets, we first found that Peroxiredoxin-1 gene (PRDX1) expression was significantly increased in human pancreatic tumors, but not in the other gastrointestinal cancers; its high expression correlated with shortened patient survival. We confirmed by immunostaining on mouse pancreata the increased Peroxiredoxin-I protein (PRX-I) expression in pancreatic neoplastic lesions and PDAC. To question the role of PRX-I in pancreatic cancer, we genetically inactivated its expression in multiple human PDAC cell lines, using siRNA and CRISPR/Cas9. In both strategies, PRX-I ablation led to reduced survival of PDAC cells. This was mainly due to an increase in the production of reactive oxygen species (ROS), accumulation of oxidative DNA damage (i.e., 8-oxoguanine), and cell cycle blockade at G2/M. Finally, we found that PRX-I ablation disrupts the autophagic flux in PDAC cells, which is essential for their survival. This proof-of-concept study supports a pro-oncogenic role for PRX-I in PDAC.


Author(s):  
Amy Larkin ◽  
Michael LaCouture ◽  
George Boutsalis ◽  
Harold Bays

Introduction: The less prominent role of triglycerides in determining cardiovascular risk keeps these lipids from being top-of-mind for practicing clinicians, yet epidemiologic data affirm that hypertriglyceridemia contributes to atherosclerotic disease development and progression. We sought to determine if online continuing medical education (CME) could improve the clinical knowledge and competence of primary care physicians (PCPs) and cardiologists regarding hypertriglyceridemia and the use of omega-3 fatty acids in its treatment. Methods: The effects of two educational interventions about advances in hypertriglyceridemia treatment (activity 1) and educating patients about omega-3 fatty acid products (activity 2) were analyzed to determine efficacy of online education presented in the form of online video-based roundtable discussions. The activities launched online in May and June, 2015 respectively, and data were collected through July, 2015. The effects of education were assessed using knowledge- and case-based matched pre-assessment/post-assessments. The effect sizes were calculated with Cohen’s d (> 0.8 is large, 0.8-0.4 is medium, and < 0.4 is small). Results: In total, 842 PCPs and 75 cardiologists who completed all pre/post assessment questions in any of the two activities during the study period were included in analyses. Significant overall improvements were seen for PCPs (activity 1: n = 452, P <.05, effect d= 0.68; activity 2: n = 390, P <.05, effect d= 0.96) and cardiologists (activity 1: n = 35, P <.05, effect d= 0.77; activity 2: n = 40, P <.05, effect d= 0.9). Compared with baseline, specific areas of improvements include: • 22% more PCPs and 31% more cardiologists identified weight loss as a nonpharmacological intervention that can effectively lower triglyceride levels for overweight/obese patients with hypertriglyceridemia, (both P < .05) • 35% more PCPs and 32% more cardiologists identified the appropriate dosing of prescription omega-3 fatty acids (both P <.05) • 23% more PCPs ( P < .05) and 20% more cardiologists ( P =.068 ) recognized that reducing the risk for pancreatitis is a primary medical objective in patients with severe elevations in triglyceride levels Areas identified as needing additional education include: • 57% of all physicians remain unaware that omega-3 fatty acids reduce apolipoprotein C3 • 61% of PCPs and 60% of cardiologists did not demonstrate a thorough understanding of the differences between prescription omega-3 fatty acids and omega-3 supplements Conclusion: This study demonstrates the success of a targeted educational intervention with two educational components on improving knowledge, competence, and clinical decision-making of PCPs and cardiologists regarding hypertriglyceridemia treatment and the role of omega-3 fatty acid products in its treatment.


2019 ◽  
Vol 287 ◽  
pp. e226
Author(s):  
N.R.T. Damasceno ◽  
F.D.C. Cartolano ◽  
G.D. Dias ◽  
A.O.C. Ventura ◽  
A.P.D.Q. Mello

2019 ◽  
Vol 35 (2) ◽  
pp. 231-241 ◽  
Author(s):  
Solomon E. Owumi ◽  
Yusuff O. Olayiwola ◽  
Gbenga E. Alao ◽  
Michael A. Gbadegesin ◽  
Oyeronke A. Odunola

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 277
Author(s):  
Jungwhoi Lee ◽  
Jungsul Lee ◽  
Woogwang Sim ◽  
Jae-Hoon Kim

Even though the tumour suppressive role of PTEN is well-known, its prognostic implications are ambiguous. The objective of this study was to further explore the function of PTEN expression in human pancreatic cancer. The expression of PTEN has been dominant in various human cancers including pancreatic cancer when compared with their matched normal tissues. The pancreatic cancer cells have been divided into PTEN blockade-susceptible and PTEN blockade-impassible groups dependent on targeting PTEN by altering intracellular signaling. The expression of PTEN has led to varying clinical outcomes of pancreatic cancer based on GEO Series (GSE) data analysis and Liptak’s z analysis. Differential dependency to PTEN blockade has been ascertained based on the expression of polo-like kinase1 PLK1 in pancreatic cancer cells. The prognostic value of PTEN also depends on PLK1 expression in pancreatic cancer. Collectively, the present study provides a rationale for targeting PTEN as a promising therapeutic strategy dependent on PLK1 expressions using a companion biomarker discovery platform.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Eun Kyoung Jeon ◽  
Young Seon Hong

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.


2015 ◽  
Vol 39 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Shima Byagowi ◽  
Taghi Naserpour Farivar ◽  
Reza Najafipour ◽  
Mehdi Sahmani ◽  
Masoud Darabi ◽  
...  

2016 ◽  
Vol 84 (2) ◽  
pp. 149-159 ◽  
Author(s):  
Simona Serini ◽  
Antonio Zinzi ◽  
Renata Ottes Vasconcelos ◽  
Elena Fasano ◽  
Maria Greca Riillo ◽  
...  

2004 ◽  
Vol 3 (2) ◽  
pp. 98-111 ◽  
Author(s):  
David H. Jho ◽  
Shawn M. Cole ◽  
Ellyn M. Lee ◽  
N. Joseph Espat

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