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- Title
Tangeretin Synergizes with 5-Fluorouracil to Induce Autophagy through MicroRNA-21 in Colorectal Cancer Cells.
- Authors
Bai, Yang; Xiong, Yao; Zhang, Yuan-Yuan; Cheng, Lin; Liu, Hui; Xu, Ke; Wu, Yi-Ying; Field, Jeffrey; Wang, Xiao-Dong; Zhou, Li-Ming
- Abstract
Combining innocuous natural products with cytotoxic agents may enhance the effectiveness of chemotherapy. Tangeretin is a citrus flavonoid that has antineoplastic properties, but its mechanism of action is still unknown. Here, we used a high throughput-screening (HTS) platform to screen for drugs that may synergize with tangeretin and confirmed the top hits against colorectal cancer (CRC) cells in vitro and in vivo. 5-Fluorouracil (5-FU) and PI3K/Akt inhibitors have come out as top hits that show a strong synergy effect with tangeretin by HTS. We further confirmed the synergistic effect of tangeretin with 5-FU against CRC cells in vitro and in vivo. Since 5-FU can increase microRNA-21 (miR-21) expression and activate PI3K/Akt signaling, we addressed if tangeretin acted at this level. In 5-FU treated cells, tangeretin inhibited miR-21 induction, rescued the expression of the target PTEN, reduced Akt activation, and induced autophagy. Together, our data indicated that a natural product, such as tangeretin, can modulate miR-21 expression and that this pathway might be a potential therapeutic target for CRC. Combining tangeretin with 5-FU may be useful in the clinic, since 5-FU is the current first line drug for treating CRC.
- Subjects
HIGH throughput screening (Drug development); REVERSE transcriptase polymerase chain reaction; FLAVONOIDS; CELL culture; COMBINATION drug therapy; XENOGRAFTS; ANALYSIS of variance; AUTOPHAGY; WESTERN immunoblotting; RNA; FLUOROURACIL; COLORECTAL cancer; GENE expression; CELLULAR signal transduction; ELECTRON microscopy; T-test (Statistics); CELL proliferation; DESCRIPTIVE statistics; RESEARCH funding; DATA analysis software; DNA damage; SENSITIVITY &; specificity (Statistics); CITRUS
- Publication
American Journal of Chinese Medicine, 2022, Vol 50, Issue 6, p1681
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X22500719