An NIR‐Fluorophore‐Based Inhibitor of SOD1 Induces Apoptosis by Targeting Transcription Cofactor PC4. Issue 5 (15th February 2019)

• Record Type: Journal Article
• Authors: Luo, Peng; Tan, Xu; Luo, Shenglin; Wang, Ziwen; Long, Lei; Wang, Yawei; Liao, Fengying; Chen, Long; Zhang, Chi; He, Jintao; Huang, Yinghui; Liu, Zujuan; Gan, Yibo; Chen, Zelin; Wang, Yang; Liu, Yunsheng; Wang, Yu; Shi, Chunmeng
• Is Part Of: Advanced therapeutics. Volume 2:Issue 5(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-02-15
• Subjects: cancer theranostics -- near‐infrared imaging -- positive cofactor 4 -- superoxide dismutase 1 (SOD1) inhibitor -- tumur‐targeted agents; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.201800148
• Languages: English
• ISSNs: 2366-3987

Abstract

Abstract: Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. Development of novel therapies has focused on new oncogenes and few tumor‐targeted theranostic agents. Recent studies show that the increased oxidative stress that results from abnormal metabolism makes cancer cells more dependent on antioxidant systems, indicating a proper therapeutic target. As a major antioxidant enzyme, superoxide dismutase 1 (SOD1) is overexpressed in cancer cells and closely related to carcinogenesis and therapeutic effects. However, there is still a lack of tumor‐targeted agents to effectively inhibit the expression of SOD1. Here, a novel near‐infrared heptamethine cyanine dye, IR‐37, is designed, synthesized, and screened that preferentially accumulates in tumor cells with an intrinsic structure‐inherent targeting property, significantly inhibits the expression of SOD1 and induces excessive reactive oxygen species (ROS)‐mediated apoptosis. IR‐37 also has excellent optical properties, implying its potential application in tumor‐targeted imaging. Moreover, a novel CRC‐related oncogene, positive cofactor 4 (PC4), is identified that is involved in the killing effects of IR‐37 through the SOD1‐ROS‐c‐Jun N‐terminal kinase (JNK) pathway. Together, these findings suggest that IR‐37 may be a promising theranostic agent for personalized tumor‐targeted therapy and imaging, and that PC4 is a novel oncogene for the diagnosis and therapy of CRC. Abstract : A near‐infrared‐fluorophore‐based SOD1 inhibitor is developed for colorectal cancer . With an intrinsic structure‐inherent tumor‐targeting property, the fluorophore significantly inhibits SOD1 expression and triggers reactive oxygen species‐mediated cell death by targeting positive cofactor 4, a novel potential therapeutic target and prognostic marker in colorectal cancer. This work may represent a promising candidate agent for personalized tumor‐targeted therapy and imaging.