3B, a novel photosensitizer, inhibits glycolysis and inflammation via miR-155-5p and breaks the JAK/STAT3/SOCS1 feedback loop in human breast cancer cells

• Published in: Biomedicine & pharmacotherapy 2016-08, Vol.82, p.141-150
• Main Authors: Lei, Kecheng, Du, Wenpei, Lin, Shengchao, Yang, Liyan, Xu, Yichun, Gao, Yuwei, Xu, Baixue, Tan, Shaoying, Xu, Yufang, Qian, Xuhong, Liang, Xin, Liu, Jianwen
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Base Sequence; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Line, Tumor; Feedback, Physiological - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Glucose; Glycolysis; Glycolysis - drug effects; Heterocyclic Compounds, 4 or More Rings - chemistry; Heterocyclic Compounds, 4 or More Rings - pharmacology; Humans; Inflammation; Inflammation - pathology; Internal Medicine; Janus Kinases - metabolism; L-Lactate Dehydrogenase - metabolism; Lactic Acid - metabolism; Medical Education; MicroRNAs - metabolism; miR-155; Models, Biological; PDT; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Signal Transduction; STAT3 Transcription Factor - metabolism; Suppressor of Cytokine Signaling Proteins - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.04.049

Abstract Compared to normal cells, most cancer cells produce ATP by glycolysis under aerobic conditions rather than via the tricarboxylic acid cycle (TCA). This study is intended to determine whether 3B, a novel photosensitizer, can inhibit glycolysis and inflammation in breast cancer cells. We showed that 3B had the ability to repress glucose consumption as well as the generation of ATP, lactate and lactate dehydrogenase. 3B-PDT not only inhibited the expression of IL-1β and IL-6 but also affected the JAK-STAT3 inflammatory pathway in vitro . The present study showed that 3B featured a significant inhibitory effect on the expression of microRNA-155-5p and SOCS1 might serve as a target gene. In vivo studies revealed that 3B inhibited tumor growth and exhibited almost no side effects. Therefore, through the anti-glycolytic effect and breakage of the JAK/STAT3/SOCS1 feedback loop via miR-155-5p, 3B may potentially serve as a potential therapeutic agent against breast cancer.