TY - JOUR
T1 - Induction of Apoptosis via Inactivating PI3K/AKT Pathway in Colorectal Cancer Cells Using Aged Chinese Hakka Stir-Fried Green Tea Extract
AU - Zhang, Xinyue
AU - Huang, Haiying
AU - Sun, Shili
AU - Li, Dongli
AU - Sun, Lingli
AU - Li, Qiuhua
AU - Chen, Ruohong
AU - Lai, Xingfei
AU - Zhang, Zhenbiao
AU - Zheng, Xi
AU - Wong, Wing Leung
AU - Wen, Shuai
N1 - Funding Information:
This study was funded by the Agricultural competitive industry discipline team building project of Guangdong Academy of Agricultural Sciences (Grant Nos. 202126TD); the Food nutrition and health Collaborative Innovation Center of GDAAS (Grant Nos. XT202229); the Guangdong Basic and Applied Basic Research Foundation (Grant Nos. 2020A1515011266, 2021A1515010958); the Guangzhou Science and Technology Plan Projects (Grant Nos. 202102020047, 202002030202, 202201011455); the Key-Area Research and Development Program of Guangdong Province (Grant Nos. 2020B0202080003); the Innovation Fund projects of Guangdong Academy of Agricultural Sciences (Grant Nos. 202115, 202035); the special fund for scientific innovation strategy-construction of high level Academy of Agriculture Science (Grant Nos. R2019PY-JX004); the Innovation Fund projects of Guangdong Key Laboratory of Tea Plant Resources Innovation and Utilization (Grant Nos. 2021CX02); and the special fund project for introduction of scientific and technological talents of Guangdong Academy of Agricultural Sciences (Grant Nos. R2021YJ-YB3014); and the special commissioner project of Nanxiong Science and Technology (Grant Nos. NO.15). The funders did not have any role in study design, data collection, or data analysis.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/12
Y1 - 2022/12
N2 - Food extract supplements, with high functional activity and low side effects, play a recognized role in the adjunctive therapy of human colorectal cancer. The present study reported a new functional beverage, which is a type of Chinese Hakka stir-fried green tea (HSGT) aged for several years. The extracts of the lyophilized powder of five HSGT samples with different aging periods were analyzed with high-performance liquid chromatography. The major components of the extract were found to include polyphenols, catechins, amino acids, catechins, gallic acid and caffeine. The tea extracts were also investigated for their therapeutic activity against human colorectal cancer cells, HT-29, an epithelial cell isolated from the primary tumor. The effect of different aging time of the tea on the anticancer potency was compared. Our results showed that, at the cellular level, all the extracts of the aged teas significantly inhibited the proliferation of HT-29 in a concentration-dependent manner. In particular, two samples prepared in 2015 (15Y, aged for 6 years) and 2019 (19Y, aged for 2 years) exhibited the highest inhibition rate for 48 h treatment (cell viability was 50% at 0.2 mg/mL). Further, all the aged tea extracts examined were able to enhance the apoptosis of HT-29 cells (apoptosis rate > 25%) and block the transition of G1/S phase (cell-cycle distribution (CSD) from <20% to >30%) population to G2/M phase (CSD from nearly 30% to nearly 10%) at 0.2 mg/mL for 24 h or 48 h. Western blotting results also showed that the tea extracts inhibited cyclin-dependent kinases 2/4 (CDK2, CDK4) and CylinB1 protein expression, as well as increased poly ADP-ribose polymerase (PRAP) expression and Bcl2-associated X (Bax)/B-cell lymphoma-2 (Bcl2) ratio. In addition, an upstream signal of one of the above proteins, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling, was found to be involved in the regulation, as evidenced by the inhibition of phosphorylated PI3K and AKT by the extracts of the aged tea. Therefore, our study reveals that traditional Chinese aged tea (HSGT) may inhibit colon cancer cell proliferation, cell-cycle progression and promoted apoptosis of colon cancer cells by inactivating PI3K/AKT signalling.
AB - Food extract supplements, with high functional activity and low side effects, play a recognized role in the adjunctive therapy of human colorectal cancer. The present study reported a new functional beverage, which is a type of Chinese Hakka stir-fried green tea (HSGT) aged for several years. The extracts of the lyophilized powder of five HSGT samples with different aging periods were analyzed with high-performance liquid chromatography. The major components of the extract were found to include polyphenols, catechins, amino acids, catechins, gallic acid and caffeine. The tea extracts were also investigated for their therapeutic activity against human colorectal cancer cells, HT-29, an epithelial cell isolated from the primary tumor. The effect of different aging time of the tea on the anticancer potency was compared. Our results showed that, at the cellular level, all the extracts of the aged teas significantly inhibited the proliferation of HT-29 in a concentration-dependent manner. In particular, two samples prepared in 2015 (15Y, aged for 6 years) and 2019 (19Y, aged for 2 years) exhibited the highest inhibition rate for 48 h treatment (cell viability was 50% at 0.2 mg/mL). Further, all the aged tea extracts examined were able to enhance the apoptosis of HT-29 cells (apoptosis rate > 25%) and block the transition of G1/S phase (cell-cycle distribution (CSD) from <20% to >30%) population to G2/M phase (CSD from nearly 30% to nearly 10%) at 0.2 mg/mL for 24 h or 48 h. Western blotting results also showed that the tea extracts inhibited cyclin-dependent kinases 2/4 (CDK2, CDK4) and CylinB1 protein expression, as well as increased poly ADP-ribose polymerase (PRAP) expression and Bcl2-associated X (Bax)/B-cell lymphoma-2 (Bcl2) ratio. In addition, an upstream signal of one of the above proteins, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling, was found to be involved in the regulation, as evidenced by the inhibition of phosphorylated PI3K and AKT by the extracts of the aged tea. Therefore, our study reveals that traditional Chinese aged tea (HSGT) may inhibit colon cancer cell proliferation, cell-cycle progression and promoted apoptosis of colon cancer cells by inactivating PI3K/AKT signalling.
KW - cell apoptosis
KW - cell-cycle arrest
KW - effect of aging time
KW - green tea extract
KW - PI3K/AKT signalling
UR - https://www.scopus.com/pages/publications/85143631142
U2 - 10.3390/molecules27238272
DO - 10.3390/molecules27238272
M3 - Journal article
C2 - 36500365
AN - SCOPUS:85143631142
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 23
M1 - 8272
ER -
