title: Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation.
abstract: The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Li
authors.affiliation: Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Experimental Animal Center, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Yang-Min
authors.initials: YM
authors.lastname: Xie
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Lian-Di
authors.initials: LD
authors.lastname: Liao
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Xiu-E
authors.initials: XE
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Fa-Min
authors.initials: FM
authors.lastname: Zeng
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Du
authors.affiliation: Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Xie
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
authors.affiliation: The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.|Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010080:Oxazoles / Q000494:pharmacology; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019012:Integrin beta1; D010080:Oxazoles; C022800:conglobatin
keywords: anoikis; cell adhesion; esophageal squamous cell carcinoma cells; macrolide analog F806; β1 integrin