Inhibitory effects of cocoa tea (Camellia ptilophylla) in human hepatocellular carcinoma HepG2 in vitro and in vivo through apoptosis.
Cocoa tea (Camellia ptilophylla), a naturally decaffeinated tea commonly consumed as a healthy beverage in southern China, has been recently found to be a potential candidate for the treatment of different diseases, including obesity and cancers. The present study aimed to evaluate the anti-liver cancer activities of green cocoa tea infusion (GCTI) in vitro and in vivo using human hepatocarcinoma cell line HepG2 cells and nude mice xenograft model. The apoptotic activities of GCTI were assessed using flow cytometry, Western blotting and immunohistochemical analysis. Our results showed that GCTI significantly inhibited the proliferation of HepG2 cells in a dose-dependent manner (IC₅₀ values=292 μg/ml at 72 h). GCTI induced HepG2 cells to undergo apoptosis, which was demonstrated by cell cycle analysis and annexin-V and propidium iodide staining. The caspase cascade was activated as shown by significant proteolytic cleavage of caspase-3 and PARP in GCTI-treated cells in a dose- and time-dependent manner. In addition, GCTI increased the expression of cell cycle inhibitory proteins (p21, p27 and p53) and the Bax-to-Bcl-2 ratio to induce apoptosis. The antiproliferative effect of GCTI was confirmed in HepG2 xenograft nude mice. The tumor growth was effectively inhibited by GCTI in a dose-dependent manner as indicated by the decrease in tumor volume and tumor weight after 4 weeks of treatment. Administration of GCTI increased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3-positive cells in the tumor section. In conclusion, these results revealed that GCTI may be a potential and promising agent of natural resource to treat liver cancer.
Department of Biology, School of Life Science, Sun Yat-sen University, Guangzhou, China.
Xiao-rong
XR
Yang
Yuan-yuan
YY
Wang
Kai-Kai
KK
La
Li
L
Peng
Xiao-hong
XH
Song
Xiang-gang
XG
Shi
Xiao-feng
XF
Zhu
Ping-chung
PC
Leung
Chun-hay
CH
Ko
Chuang-xing
CX
Ye
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D028244:Camellia / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000178:diet therapy* / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D002470:Cell Survival; D019587:Dietary Supplements / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000178:diet therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; D010936:Plant Extracts