TY - JOUR
T1 - Plectalibertellenone A suppresses colorectal cancer cell motility and glucose metabolism by targeting TGF-β/Smad and Wnt pathways
AU - Gamage, Chathurika D.B.
AU - Kim, Jeong Hyeon
AU - Zhou, Rui
AU - Park, So Yeon
AU - Pulat, Sultan
AU - Varlı, Mücahit
AU - Nam, Sang Jip
AU - Kim, Hangun
N1 - Publisher Copyright:
© 2024 International Union of Biochemistry and Molecular Biology.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Colorectal cancer (CRC) is the second most common cause of cancer-related death and represents a serious worldwide health problem. CRC metastasis decreases the survival rate of cancer patients, underscoring the need to identify novel anticancer agents and therapeutic targets. Here, we introduce Plectalibertellenone A (B) as a promising agent for the inhibition of CRC cell motility and glucose metabolism and explore its mechanism of action in CRC cells. Plectalibertellenone A suppressed TGF-β gene expression and the activation of the TGF-β/Smad signaling pathway, leading to reverse epithelial to mesenchymal transition (EMT) by modulating the expressions of EMT markers and transcriptional factors such as E-cadherin, N-cadherin, vimentin, Slug, Snail, Twist, and ZEB1/2. Furthermore, disruption of Wnt signaling inhibited CRC motility and glucose metabolism including glycolysis and oxidative phosphorylation, primarily affecting glycolytic enzymes, GLUT1, HK2, PKM2, LDHA, and HIF-1α under hypoxic condition. Therefore, Plectalibertellenone A is a potential drug candidate that can be developed into a promising anticancer treatment to prevent CRC metastasis and inhibit glucose metabolism.
AB - Colorectal cancer (CRC) is the second most common cause of cancer-related death and represents a serious worldwide health problem. CRC metastasis decreases the survival rate of cancer patients, underscoring the need to identify novel anticancer agents and therapeutic targets. Here, we introduce Plectalibertellenone A (B) as a promising agent for the inhibition of CRC cell motility and glucose metabolism and explore its mechanism of action in CRC cells. Plectalibertellenone A suppressed TGF-β gene expression and the activation of the TGF-β/Smad signaling pathway, leading to reverse epithelial to mesenchymal transition (EMT) by modulating the expressions of EMT markers and transcriptional factors such as E-cadherin, N-cadherin, vimentin, Slug, Snail, Twist, and ZEB1/2. Furthermore, disruption of Wnt signaling inhibited CRC motility and glucose metabolism including glycolysis and oxidative phosphorylation, primarily affecting glycolytic enzymes, GLUT1, HK2, PKM2, LDHA, and HIF-1α under hypoxic condition. Therefore, Plectalibertellenone A is a potential drug candidate that can be developed into a promising anticancer treatment to prevent CRC metastasis and inhibit glucose metabolism.
KW - CRC
KW - EMT
KW - Plectalibertellenone A (B)
KW - aerobic glycolysis
KW - motility
KW - oxidative phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=85204487606&partnerID=8YFLogxK
U2 - 10.1002/biof.2120
DO - 10.1002/biof.2120
M3 - Article
C2 - 39291722
AN - SCOPUS:85204487606
SN - 0951-6433
VL - 51
JO - BioFactors
JF - BioFactors
IS - 1
M1 - e2120
ER -