TY - JOUR
T1 - Eugenol and capsaicin exhibit anti-metastatic activity
T2 - Via modulating TGF-β signaling in gastric carcinoma
AU - Sarkar, Arnab
AU - Das, Subrata
AU - Rahaman, Ashikur
AU - Das Talukdar, Anupam
AU - Bhattacharjee, Shamee
AU - Mandal, Deba Prasad
N1 - Publisher Copyright:
© 2020 Royal Society of Chemistry. All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - The transforming growth factor-β (TGF-β) signaling is considered to be a key player in gastric cancer metastasis, and the inhibition of the TGF-β/SMAD4 signaling pathway may be a novel strategy for therapeutic interventions in cancer. Here, the anti-metastatic activity of two phytochemicals, eugenol and capsaicin, has been studied, and their potential to antagonize TGF-β has been investigated in gastric cancer cells. Both the phytochemicals exhibited anti-metastatic activity by inhibiting the TGF-β signaling pathway independent of P21 or P53, with capsaicin proving to be more potent than eugenol. However, unlike eugenol, the inhibitory effect of capsaicin on the TGF-β signaling pathway and metastasis was found to be dependent on SMAD4, which was validated in SMAD4-knocked down AGS cell and SMAD4-null SW620 cell line. Furthermore, the use of recombinant TGF-β and TGF-β receptor inhibitor LY2109761 confirmed that the anti-metastatic activity of eugenol is partially and that of capsaicin is principally mediated through the TGF-β signaling pathway. Identifying phytochemicals with the potential to inhibit cancer metastasis by targeting the TGF-β signaling pathway has immense scope for developing a therapeutic strategy against cancer metastasis.
AB - The transforming growth factor-β (TGF-β) signaling is considered to be a key player in gastric cancer metastasis, and the inhibition of the TGF-β/SMAD4 signaling pathway may be a novel strategy for therapeutic interventions in cancer. Here, the anti-metastatic activity of two phytochemicals, eugenol and capsaicin, has been studied, and their potential to antagonize TGF-β has been investigated in gastric cancer cells. Both the phytochemicals exhibited anti-metastatic activity by inhibiting the TGF-β signaling pathway independent of P21 or P53, with capsaicin proving to be more potent than eugenol. However, unlike eugenol, the inhibitory effect of capsaicin on the TGF-β signaling pathway and metastasis was found to be dependent on SMAD4, which was validated in SMAD4-knocked down AGS cell and SMAD4-null SW620 cell line. Furthermore, the use of recombinant TGF-β and TGF-β receptor inhibitor LY2109761 confirmed that the anti-metastatic activity of eugenol is partially and that of capsaicin is principally mediated through the TGF-β signaling pathway. Identifying phytochemicals with the potential to inhibit cancer metastasis by targeting the TGF-β signaling pathway has immense scope for developing a therapeutic strategy against cancer metastasis.
UR - http://www.scopus.com/inward/record.url?scp=85094220245&partnerID=8YFLogxK
U2 - 10.1039/d0fo00887g
DO - 10.1039/d0fo00887g
M3 - Article
C2 - 33016967
AN - SCOPUS:85094220245
SN - 2042-6496
VL - 11
SP - 9020
EP - 9034
JO - Food and Function
JF - Food and Function
IS - 10
ER -