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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Dec 11

PMID 36500365

Authors

Xinyue Zhang

Haiying Huang

Shili Sun

Dongli Li

Lingli Sun

Qiuhua Li

Ruohong Chen

Xingfei Lai

Zhenbiao Zhang

Xi Zheng

Wing-Leung Wong

Shuai Wen

Affiliations

Soon will be listed here.

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.

Citing Articles

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

Qiu Z, Liao J, Chen J, Chen P, Sun B, Li A Foods. 2023; 12(10).

PMID: 37238885 PMC: 10217579. DOI: 10.3390/foods12102067.

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

Mizoguchi E, Sadanaga T, Okada T, Minagawa T, Akiba J Intest Res. 2023; 21(3):306-317.

PMID: 37072923 PMC: 10397549. DOI: 10.5217/ir.2022.00118.

References

Tan X, Gong L, Li X, Zhang X, Sun J, Luo X . Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway. Biomed Pharmacother. 2021; 143:112174. DOI: 10.1016/j.biopha.2021.112174. View

Jeng K, Chen C, Fang Y, Hou R, Chen Y . Effect of microbial fermentation on content of statin, GABA, and polyphenols in Pu-Erh tea. J Agric Food Chem. 2007; 55(21):8787-92. DOI: 10.1021/jf071629p. View

Biller L, Schrag D . Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021; 325(7):669-685. DOI: 10.1001/jama.2021.0106. View

Luo K, Xia J, Cheng B, Gao H, Fu L, Luo X . Tea polyphenol EGCG inhibited colorectal-cancer-cell proliferation and migration via downregulation of STAT3. Gastroenterol Rep (Oxf). 2021; 9(1):59-70. PMC: 7962736. DOI: 10.1093/gastro/goaa072. View

Bocchetti M, Ferraro M, Ricciardiello F, Ottaiano A, Luce A, Cossu A . The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer. Int J Mol Sci. 2021; 22(8). PMC: 8068787. DOI: 10.3390/ijms22083967. View

Chen J, Zhang L, Li C, Chen R, Liu C, Chen M . Lipophilized Epigallocatechin Gallate Derivative Exerts Anti-Proliferation Efficacy through Induction of Cell Cycle Arrest and Apoptosis on DU145 Human Prostate Cancer Cells. Nutrients. 2020; 12(1). PMC: 7020104. DOI: 10.3390/nu12010092. View

Han Y, Mun J, Jeon H, Kee J, Hong S . Betulin Inhibits Lung Metastasis by Inducing Cell Cycle Arrest, Autophagy, and Apoptosis of Metastatic Colorectal Cancer Cells. Nutrients. 2020; 12(1). PMC: 7019271. DOI: 10.3390/nu12010066. View

Lian G, Chen S, OuYang M, Li F, Chen L, Yang J . Colon Cancer Cell Secretes EGF to Promote M2 Polarization of TAM Through EGFR/PI3K/AKT/mTOR Pathway. Technol Cancer Res Treat. 2019; 18:1533033819849068. PMC: 6535704. DOI: 10.1177/1533033819849068. View

Uesato S, Kitagawa Y, Kamishimoto M, Kumagai A, Hori H, Nagasawa H . Inhibition of green tea catechins against the growth of cancerous human colon and hepatic epithelial cells. Cancer Lett. 2001; 170(1):41-4. DOI: 10.1016/s0304-3835(01)00571-7. View

10.

Zaborowski A, Abdile A, Adamina M, Aigner F, dAllens L, Allmer C . Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review. JAMA Surg. 2021; 156(9):865-874. DOI: 10.1001/jamasurg.2021.2380. View

11.

Gao X, Li X, Ho C, Lin X, Zhang Y, Li B . Cocoa tea (Camellia ptilophylla) induces mitochondria-dependent apoptosis in HCT116 cells via ROS generation and PI3K/Akt signaling pathway. Food Res Int. 2020; 129:108854. DOI: 10.1016/j.foodres.2019.108854. View

12.

Xu P, Chen L, Wang Y . Effect of storage time on antioxidant activity and inhibition on α-Amylase and α-Glucosidase of white tea. Food Sci Nutr. 2019; 7(2):636-644. PMC: 6493899. DOI: 10.1002/fsn3.899. View

13.

Lee H, Kim K, Sung J, Nam M, Suh K, Kim J . PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells. Cancers (Basel). 2020; 12(9). PMC: 7564416. DOI: 10.3390/cancers12092500. View

14.

Tan X, Hu D, Li S, Han Y, Zhang Y, Zhou D . Differences of four catechins in cell cycle arrest and induction of apoptosis in LoVo cells. Cancer Lett. 2000; 158(1):1-6. DOI: 10.1016/s0304-3835(00)00445-6. View

15.

Li Q, Lai X, Sun L, Cao J, Ling C, Zhang W . Antiobesity and anti-inflammation effects of Hakka stir-fried tea of different storage years on high-fat diet-induced obese mice model via activating the AMPK/ACC/CPT1 pathway. Food Nutr Res. 2020; 64. PMC: 7286352. DOI: 10.29219/fnr.v64.1681. View

16.

Gelibter A, Caponnetto S, Urbano F, Emiliani A, Scagnoli S, Sirgiovanni G . Adjuvant chemotherapy in resected colon cancer: When, how and how long?. Surg Oncol. 2019; 30:100-107. DOI: 10.1016/j.suronc.2019.06.003. View

17.

Li F, Lu Q, Li M, Yang X, Xiong C, Yang B . Comparison and Risk Assessment for Trace Heavy Metals in Raw Pu-erh Tea with Different Storage Years. Biol Trace Elem Res. 2019; 195(2):696-706. DOI: 10.1007/s12011-019-01886-1. View

18.

Bars-Cortina D, Sakhawat A, Pinol-Felis C, Motilva M . Chemopreventive effects of anthocyanins on colorectal and breast cancer: A review. Semin Cancer Biol. 2020; 81:241-258. DOI: 10.1016/j.semcancer.2020.12.013. View

19.

DU B, Lin P, Lin J . EGCG and ECG induce apoptosis and decrease autophagy via the AMPK/mTOR and PI3K/AKT/mTOR pathway in human melanoma cells. Chin J Nat Med. 2022; 20(4):290-300. DOI: 10.1016/S1875-5364(22)60166-3. View

20.

Cheng L, Wang Y, Zhang J, Zhu J, Liu P, Xu L . Dynamic changes of metabolic profile and taste quality during the long-term aging of Qingzhuan Tea: The impact of storage age. Food Chem. 2021; 359:129953. DOI: 10.1016/j.foodchem.2021.129953. View