TY - JOUR
T1 - EGCG sensitizes chemotherapeutic-induced cytotoxicity by targeting the ERK pathway in multiple cancer cell lines
AU - Wei, Ran
AU - Wirkus, Joanna
AU - Yang, Zixuan
AU - Machuca, Jazmin
AU - Esparza, Yasmin
AU - Mackenzie, Gerardo G.
PY - 2020/10/15
Y1 - 2020/10/15
N2 - Epigallocatechin-3-gallate (EGCG), a major polyphenol component of green tea, presents anticancer efficacy. However, its exact mechanism of action is not known. In this study, we evaluated the effect of EGCG alone or in combination with current chemotherapeutics [gemcitabine, 5-flourouracil (5-FU), and doxorubicin] on pancreatic, colon, and lung cancer cell growth, as well as the mechanisms involved in the combined action. EGCG reduced pancreatic, colon, and lung cancer cell growth in a concentration and time-dependent manner. EGCG strongly induced apoptosis and blocked cell cycle progression. Moreover, EGCG enhanced the growth inhibitory effect of 5-FU and doxorubicin. Of note, EGCG enhanced 5-FU's and doxorubicin's effect on apoptosis, but not on cell cycle. Mechanistically, EGCG reduced ERK phosphorylation concentration-dependently, and sensitized gemcitabine, 5-FU, and doxorubicin to further suppress ERK phosphorylation in multiple cancer cell lines. In conclusion, EGCG presents a strong anticancer effect in pancreatic, colon, and lung cancer cells and is a robust combination partner for multiple chemotherapeutics as evidenced by reducing cancer cell growth, in part, by inhibiting the ERK pathway.
AB - Epigallocatechin-3-gallate (EGCG), a major polyphenol component of green tea, presents anticancer efficacy. However, its exact mechanism of action is not known. In this study, we evaluated the effect of EGCG alone or in combination with current chemotherapeutics [gemcitabine, 5-flourouracil (5-FU), and doxorubicin] on pancreatic, colon, and lung cancer cell growth, as well as the mechanisms involved in the combined action. EGCG reduced pancreatic, colon, and lung cancer cell growth in a concentration and time-dependent manner. EGCG strongly induced apoptosis and blocked cell cycle progression. Moreover, EGCG enhanced the growth inhibitory effect of 5-FU and doxorubicin. Of note, EGCG enhanced 5-FU's and doxorubicin's effect on apoptosis, but not on cell cycle. Mechanistically, EGCG reduced ERK phosphorylation concentration-dependently, and sensitized gemcitabine, 5-FU, and doxorubicin to further suppress ERK phosphorylation in multiple cancer cell lines. In conclusion, EGCG presents a strong anticancer effect in pancreatic, colon, and lung cancer cells and is a robust combination partner for multiple chemotherapeutics as evidenced by reducing cancer cell growth, in part, by inhibiting the ERK pathway.
KW - 5-FU
KW - Colon cancer
KW - Doxorubicin
KW - Epigallocatechin-3-gallate
KW - ERK
KW - Gemcitabine
KW - Lung cancer
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85089738618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089738618&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2020.108546
DO - 10.1016/j.abb.2020.108546
M3 - Article
C2 - 32818507
AN - SCOPUS:85089738618
VL - 692
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
M1 - 108546
ER -