Induction of apoptosis via inactivating PI3K/AKT pathway in colorectal cancer cells with the aged Hakka stir-fried green tea

Abstract

Abstract Human colorectal cancer is notorious for its high morbidity and mortality; however, the lack of effective and low-toxic drugs has currently been a bottleneck for the treatment of the disease. The present study reported a new functional food of Hakka stir-fried green tea (HSGT) aged with different years, including those stored starting from 2003 (03Y), 2007 (07Y), 2011 (11Y), 2015 (15Y) and 2019 (19Y) respectively, for their effective therapeutic activity against colorectal cancer. The major active ingredients including polyphenols, catechins, amino acids, catechins, gallic acid and caffeine found in the lyophilized powder of these aged HSGT were analyzed with high performance liquid chromatography. Our results showed that, at the cellular level, all these aged HSGT inhibited significantly the proliferation of colon cancer cells (HT-29) in a concentration-dependent manner. In particular, the batch of 15Y and 19Y exhibited the highest inhibition rate for 48 hours treatment. Further, all these aged HSGT examined were able to enhance the apoptosis of HT-29 cells and block the transition of G1/S phase population to G2/M phase. Western blotting results also showed that the aged HSGT inhibited CDK2, CDK4 and CylinB1 protein expression, as well as increased PRAP expression and Bax/Bcl2 ratio in HT-29 cells. In addition, an upstream signal, PI3K/AKT signaling, was found involving in this regulation, as evidenced by the inhibition of phosphorylated PI3K and AKT by the aged HSGT. Therefore, our study reveals that the aged HSGT may inhibit colon cancer cell proliferation, cell cycle progression and promoted apoptosis of colon cancer cells by inactivating PI3K/AKT signalling. The therapeutic effects of the HSGT aged with different years were also investigated.