Research Papers:

HS-133, a novel fluorescent phosphatidylinositol 3-kinase inhibitor as a potential imaging and anticancer agent for targeted therapy

Ju-Hee Lee _, Kyung Hee Jung, Hyunseung Lee, Mi Kwon Son, Sun-Mi Yun, Sung-Hoon Ahn, Kyeong-Ryoon Lee, Soyoung Lee, Donghee Kim, Sungwoo Hong and Soon-Sun Hong

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Oncotarget. 2014; 5:10180-10197. https://doi.org/10.18632/oncotarget.2507

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Ju-Hee Lee1,*, Kyung Hee Jung1,*, Hyunseung Lee1, Mi Kwon Son1, Sun-Mi Yun1, Sung-Hoon Ahn2, Kyeong-Ryoon Lee2, Soyoung Lee3, Donghee Kim3, Sungwoo Hong3, Soon-Sun Hong1

1Department of Drug Development, College of Medicine, Inha University, Incheon, Republic of Korea

2Drug Discovery Platform Technology Team, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea

3Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS) and Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

*These authors equally contributed to this work

Correspondence to:

Soon-Sun Hong, e-mail: [email protected]

Sungwoo Hong, e-mail: [email protected]

Keywords: Anticancer, Targeted therapy, PI3K, Fluorescence, Imaging, Apoptosis

Received: June 09, 2014     Accepted: August 16, 2014     Published: September 29, 2014


As PI3K/Akt signaling is frequently deregulated in a wide variety of human tumors, PI3K inhibitors are an emerging class of drugs for cancer treatment. The monitoring of the drug behavior and distribution in the biological system can play an important role for targeted therapy and provide information regarding the response or resistance to available therapies. In this study, therefore, we have developed a family of xanthine derivatives, serving as a dual function exhibiting fluorescence, as well as inhibiting PI3K. Among them, HS-133 showed anti-proliferative effects and was monitored for its subcellular localization by a fluorescence microscopy. HS-133 suppressed the PI3K/Akt pathway and induced cell cycle arrest at the G0/G1 phase. The induction of apoptosis by HS-133 was confirmed by the increases of the cleaved PARP, caspase-3, and caspase-8. Furthermore, HS-133 decreased the protein expression of HIF-1α and VEGF, as well inhibited the tube formation and migration of the human umbilical vein endothelial cells. In vivo imaging also showed that tumors were visualized fluorescent with HS-133, and its oral administration significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Thus, we suggest that HS-133 may be used as a fluorescent anticancer agent against human breast cancer.

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