Flavonoids Luteolin and Quercetin Inhibit RPS19 and contributes to metastasis of cancer cells through c-Myc reduction

Ku-Chung Chen; Wen-Hsien Hsu; Jhih-Yun Ho; Cheng-Wei Lin; Cheng-Ying Chu; Chithan C Kandaswami; Ming-Ting Lee; Chia-Hsiung Cheng

doi:10.1016/j.jfda.2018.01.012

Flavonoids Luteolin and Quercetin Inhibit RPS19 and contributes to metastasis of cancer cells through c-Myc reduction

J Food Drug Anal. 2018 Jul;26(3):1180-1191. doi: 10.1016/j.jfda.2018.01.012. Epub 2018 Feb 13.

Authors

Ku-Chung Chen^{1

2}, Wen-Hsien Hsu^{1

3}, Jhih-Yun Ho², Cheng-Wei Lin^{1

2}, Cheng-Ying Chu⁴, Chithan C Kandaswami⁵, Ming-Ting Lee⁶, Chia-Hsiung Cheng^{1

2}

Affiliations

¹ Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Department of Surgery, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁴ Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Castle Hills Health, Coimbatore, India.
⁶ Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

Abstract

Flavonoids luteolin and quercetin can inhibit growth and metastasis of cancer cells. In our previous report, luteolin and quercetin was shown to block Akt/mTOR/c-Myc signaling. Here, we found luteolin and quercetin reduced protein level and transactivation activity of RPS19 in A431-III cells, which is isolated from parental A431 (A431-P) cell line. Further investigation the inhibitory mechanism of luteolin and quercetin on RPS19, we found c-Myc binding sites on RPS19 promoter. The Akt inhibitor LY294002, mTOR inhibitor rapamycin and c-Myc inhibitor 10058-F4 significantly suppressed RPS19 expression and transactivation activities. Overexpression and knockdown of c-Myc in cancer cells show RPS19 expression was regulated by c-Myc. Furthermore, Knockdown and overexpression of RPS19 was used to analyze of the function of RPS19 in cancer cells. The epithelial-mesenchymal transition (EMT) markers and metastasis abilities of cancer cells were also regulated by RPS19. These data suggest that luteolin and quercetin might inhibit metastasis of cancer cells by blocking Akt/mTOR/c-Myc signaling pathway to suppress RPS19-activated EMT signaling.

Keywords: EMT; Luteolin; Quercetin; RPS19; c-Myc.

Publication types

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

MeSH terms

Cell Line, Tumor
Epithelial-Mesenchymal Transition / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Luteolin / pharmacology*
Neoplasm Metastasis
Neoplasms / genetics
Neoplasms / metabolism*
Neoplasms / pathology
Neoplasms / physiopathology
Oncogene Protein v-akt / genetics
Oncogene Protein v-akt / metabolism
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism*
Quercetin / pharmacology*
Ribosomal Proteins / genetics
Ribosomal Proteins / metabolism*
Signal Transduction / drug effects
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism

Substances

MYC protein, human
Proto-Oncogene Proteins c-myc
Ribosomal Proteins
ribosomal protein S19
Quercetin
MTOR protein, human
Oncogene Protein v-akt
TOR Serine-Threonine Kinases
Luteolin

Grants and funding

This work was supported by Taipei Medical University-Wan Fang Hospital (104TMU-WFH-08) and the Ministry of Science and Technology, Taiwan (MOST106-2314-B-038-028).