TY - JOUR
T1 - Brevilin A exerts anti-colorectal cancer effects and potently inhibits STAT3 signaling in vitro
AU - Meng, Mingjing
AU - Tan, Jincheng
AU - Chen, Hui
AU - Shi, Zhiqiang
AU - Kwan, Hiu-Yee
AU - Su, Tao
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China ( 82074019 , 82274158 ), Young Elite Scientists Sponsorship Program by CAST ( 2021-QNRC2-B15 ), Guangzhou Basic and Applied Basic Research Project ( 202201011503 ), the open project of State Key Laboratory of Quality Research in Chinese Medicine ( Macau University of Science and Technology , SKL-QRCM(MUST)-2020-2022 , 2R2103 ), FNRA-IG ( RC-FNRA-IG/20-21/SCM/01 ), HMRF ( 08193596 ), Shenzhen Virtual University Park Special Fund Project ( 2021Szvup131 ), GDNSF ( 2021A1515010655 ) and ITC ( PRP/015/19FX ), Guangdong Basic and Applied Basic Research Foundation ( 2020B1515130005 ), and the Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research , Guangzhou University of Chinese Medicine ( 2020B1212030006 ).
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/8
Y1 - 2023/8
N2 - Colorectal cancer (CRC) is the third most common cause of cancer-related morbidity worldwide, with an estimated of 1.85 million new cases and 850,000 deaths every year. Nevertheless, the current treatment regimens for CRC have many disadvantages, including toxicities and off-targeted side effects. STAT3 (signal transducer and activator of transcription 3) has been considered as a promising molecular target for CRC therapy. Brevilin A, a sesquiterpene lactone compound rich in Centipedae Herba has potent anticancer effects in nasopharyngeal, prostate and breast cancer cells by inhibiting the STAT3 signaling. However, the anti-CRC effect of brevilin A and the underlying mechanism of action have not been fully elucidated. In this study, we aimed to investigate the involvement of STAT3 signaling in the anti-CRC action of brevilin A. Here, HCT-116 and CT26 cell models were used to investigate the anti-CRC effects of brevilin A in vitro. HCT-116 cells overespressing with STAT3 were used to evaluate the involvement of STAT3 signaling in the anti-CRC effect of brevilin A. Screening of 49 phosphorylated tyrosine kinases in the HCT-116 cells after brevilin A treatment was performed by using the human phospho-receptor tyrosine kinase (phospho-RTK) array. Results showed that brevilin A inhibited cell proliferation and cell viability, induced apoptosis, reduced cell migration and invasion, inhibited angiogenesis, lowered the protein expression levels of phospho-Src (Tyr416), phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and inhibited STAT3 activation and nuclear localization. Brevilin A also significantly reduced the protein expression levels of STAT3 target genes, such as MMP-2, VEGF and Bcl-xL. More importantly, over-activation of STAT3 diminished brevilin A's effects on cell viability. All these results suggest that brevilin A exerts potent anti-CRC effects, at least in part, by inhibiting STAT3 signaling. Our findings provide a strong pharmacological basis for the future exploration and development of brevilin A as a novel STAT3-targeting phytotherapeutic agent for CRC treatment.
AB - Colorectal cancer (CRC) is the third most common cause of cancer-related morbidity worldwide, with an estimated of 1.85 million new cases and 850,000 deaths every year. Nevertheless, the current treatment regimens for CRC have many disadvantages, including toxicities and off-targeted side effects. STAT3 (signal transducer and activator of transcription 3) has been considered as a promising molecular target for CRC therapy. Brevilin A, a sesquiterpene lactone compound rich in Centipedae Herba has potent anticancer effects in nasopharyngeal, prostate and breast cancer cells by inhibiting the STAT3 signaling. However, the anti-CRC effect of brevilin A and the underlying mechanism of action have not been fully elucidated. In this study, we aimed to investigate the involvement of STAT3 signaling in the anti-CRC action of brevilin A. Here, HCT-116 and CT26 cell models were used to investigate the anti-CRC effects of brevilin A in vitro. HCT-116 cells overespressing with STAT3 were used to evaluate the involvement of STAT3 signaling in the anti-CRC effect of brevilin A. Screening of 49 phosphorylated tyrosine kinases in the HCT-116 cells after brevilin A treatment was performed by using the human phospho-receptor tyrosine kinase (phospho-RTK) array. Results showed that brevilin A inhibited cell proliferation and cell viability, induced apoptosis, reduced cell migration and invasion, inhibited angiogenesis, lowered the protein expression levels of phospho-Src (Tyr416), phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and inhibited STAT3 activation and nuclear localization. Brevilin A also significantly reduced the protein expression levels of STAT3 target genes, such as MMP-2, VEGF and Bcl-xL. More importantly, over-activation of STAT3 diminished brevilin A's effects on cell viability. All these results suggest that brevilin A exerts potent anti-CRC effects, at least in part, by inhibiting STAT3 signaling. Our findings provide a strong pharmacological basis for the future exploration and development of brevilin A as a novel STAT3-targeting phytotherapeutic agent for CRC treatment.
KW - Brevilin A
KW - Colorectal cancer
KW - STAT3 signaling
KW - Apoptosis
KW - Migration
KW - Invasion
UR - http://www.scopus.com/inward/record.url?scp=85166541976&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2023.e18488
DO - 10.1016/j.heliyon.2023.e18488
M3 - Journal article
AN - SCOPUS:85166541976
SN - 2405-8440
VL - 9
JO - Heliyon
JF - Heliyon
IS - 8
M1 - e18488
ER -