Induction of Apoptosis via Inactivating PI3K/AKT Pathway in Colorectal Cancer Cells Using Aged Chinese Hakka Stir-Fried Green Tea Extract

Abstract

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.

Does caffeine have a double-edged sword role in inflammation and carcinogenesis in the colon?

“…[81][82][83][84][85][86] An association between coffee/CAF consumption and colonic tumorigenesis has been summarized in Table 2. [87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] Within this table, about 84% of studies showed the beneficial effects of coffee/CAF intake for CRC development among the various type of studies. Still, the remaining less than 20% of studies show the opposite or inconclusive effects.…”

“…An association between coffee/CAF consumption and colonic tumorigenesis has been summarized in Table 2 [ 87 - 102 ]. Within this table, about 84% of studies showed the beneficial effects of coffee/CAF intake for CRC development among the various type of studies.…”

The Cultivar Effect on the Taste and Aroma Substances of Hakka Stir-Fried Green Tea from Guangdong

“…Its success as a beverage can be attributed to its excellent health benefits, unique and stimulating tastes, and pleasant aromas [1][2][3]. Hakka stir-fried green tea (HSGT) is a type of roasted green tea from Guangdong, China [4]. The unique "fried rice aroma" and "sweet taste" are popular in the local Chinese Hakka market, as well as in the markets of the overseas Hakka diaspora, tea connoisseurs, and emerging tea novices [5].…”