RETRACTED ARTICLE: A novel small-molecule inhibitor suppresses colon cancer metastasis through inhibition of metastasis-
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PRECLINICAL STUDIES
A novel small-molecule inhibitor suppresses colon cancer metastasis through inhibition of metastasis-associated in colon cancer-1 transcription Xue-Feng Jiang 1 & Zhen Tian 2 & Shuang-Xi Zhu 3 & Sui-Hui Li 4 & Yu Sun 5 Received: 10 March 2020 / Accepted: 21 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary We previously reported that the metastasis-associated in colon cancer-1 (MACC-D1) is overexpressed in colon cancer. However, so far, only a few effective MACC-1 inhibitors have been identified. To discover novel transcriptional inhibitors of MACC-1, we performed a luciferase reporter-based high-throughput screening (HTS). This strategy discovered rottlerin as an inhibitor of MACC-1 transcription was able to reduce cell motility in colon cancer in time- and dose-dependent manners. Wound healing assay indicated that 48-h treatment with 2.5 μM rottlerin impairs wound closure compared to the controls. Electrophoretic mobility shift assays showed that rottlerin inhibits the binding of the transcriptional activators Sp1 and c-Jun with human MACC-1 promoter. A combination of Western blot assays and expression analyses by qRT-PCR ruled out that rottlerin may act indirectly through inhibition of c-Jun or Sp1 expression to decrease MACC-1 expression in human colon cancer cell lines SW620. Rather, these results support that rottlerin restricts the binding of MACC-1 promoter directly by c-Jun and Sp1 in colon cancer cells. Thus, as a small-molecule inhibitor of MACC-1, rottlerin may benefit colon cancer patients by suppressing MACC1-dependent tumor growth and metastasis. Keywords High-throughput screening . Colon cancer . MACC-1 promoter . Tumor metastasis
Introduction Colon cancer is one of the most aggressive human malignancies and a leading cause of cancer-related mortality worldwide [1]. Surgery is the best choice for colon cancer therapy, but the occurrence of post-surgical metastases remains high due to
* Yu Sun [email protected] 1
Department of Gastroenterology, The Third Hospital of Jilin University, Changchun 130033, China
2
Department of Cardiology, The Third Hospital of Jilin University, Changchun 130033, China
3
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-sen University & Guangdong Key Laboratory of Stomatology, Guangzhou, China
4
Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
5
Department of Interventional Radiology, The Third Hospital of Jilin University, Changchun 130033, China
cancer cells’ migration and invasion of tumor-surrounding tissues and distal organs [2, 3]. Hence, blocking metastasis formation is crucial to achieve colon cancer therapy. Recent studies indicated that colorectal cancer metastases might be triggered by the oncogene metastasis-associated in colon cancer-1 (MACC-1; UniProt: Q6ZN28). MACC-1 is overexpressed in primary and metastatic colon cancers compared to healthy colon tissues or adenomas [2]. MACC-1 is also
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