Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells

Meiyu Peng; Bingqing Huang; Qi Zhang; Shuyu Fu; Dan Wang; Xixi Cheng; Xi Wu; Zhenyi Xue; Lijuan Zhang; Da Zhang; Yurong Da; Yun Dai; Qing Yang; Zhi Yao; Liang Qiao; Rongxin Zhang

doi:10.1016/j.canlet.2014.08.011

Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells

Cancer Lett. 2014 Nov 28;354(2):407-16. doi: 10.1016/j.canlet.2014.08.011. Epub 2014 Aug 13.

Authors

Meiyu Peng¹, Bingqing Huang², Qi Zhang³, Shuyu Fu², Dan Wang², Xixi Cheng², Xi Wu², Zhenyi Xue², Lijuan Zhang², Da Zhang⁴, Yurong Da², Yun Dai⁵, Qing Yang⁶, Zhi Yao², Liang Qiao⁷, Rongxin Zhang⁸

Affiliations

¹ Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Weifang Medical University, Weifang, China.
² Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
³ Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
⁴ School of Medical Imaging, Tianjin Medical University, Tianjin 300070, China.
⁵ Department of Gastroenterology, Peking University First Hospital, Beijing, China.
⁶ Department of Genitourinary Oncology, Tianjin Medical University Cancer Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
⁷ Storr Liver Unit, Westmead Millennium Institute, The Western Clinical School of the University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. Electronic address: [email protected].
⁸ Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China. Electronic address: [email protected].

PMID: 25128650
DOI: 10.1016/j.canlet.2014.08.011

Abstract

Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways. Embelin substantially reduced the tumorigenicity of pancreatic cancer cells in vivo, which was associated with reduced inflammatory cells and immune suppressive cells, IL-17A(+) Th17, GM-CSF(+) Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover, embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin represents a novel therapeutic drug candidate for the clinical treatment of pancreatic cancer.

Keywords: Embelin; IL-6; Inflammation; MDSCs; Pancreatic cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Benzoquinones / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Disease Models, Animal
Disease Progression
Down-Regulation
Female
Inflammation / drug therapy
Inflammation / immunology
Inflammation / pathology
Interleukin-6 / immunology*
Interleukin-6 / metabolism
Mice
Mice, Inbred C57BL
Pancreatic Neoplasms / drug therapy*
Pancreatic Neoplasms / immunology*
Pancreatic Neoplasms / pathology
STAT3 Transcription Factor / metabolism
T-Lymphocytes, Regulatory / drug effects
T-Lymphocytes, Regulatory / immunology
Tumor Suppressor Protein p53 / metabolism

Substances

Benzoquinones
Interleukin-6
STAT3 Transcription Factor
Stat3 protein, mouse
Tumor Suppressor Protein p53
embelin