Pyrogallol induces G2-M arrest in human lung cancer cells and inhibits tumor growth in an animal model.
Pyrogallol, a catechin compound, is an active component of Emblica officinalis extracts and has an anti-proliferative effect on some human cancer cell lines. In our preliminary study, pyrogallol had highly cytotoxic effect on human lung cancer cell lines and less effect on human bronchial epithelium cell line. This study was performed to investigate the beneficial effect of pyrogallol on human lung cancer cell lines - H441 (lung adenocarcinoma) and H520 (lung squamous cell carcinoma). The MTT (cytotoxic) data showed the inhibition growth of lung cancer cells followed pyrogallol treatment. The cell cycle of lung cancer cells was arrested in G2/M phase using flow cytometry. Using Western blot analysis, the cell cycle related proteins - cyclin B1 and Cdc25c were decreased in a time-dependent manner and the phosphorylated Cdc2 (Thr14) was increased within 4h pyrogallol treatment. Moreover, the higher cleavage of poly (ADP)-ribose polymerase (PARP), the increased of Bax concurrent with the decreased of Bcl-2 indicated that pyrogallol treatment resulted in apoptosis of lung cancer cells. The cell apoptosis was also directly demonstrated using Annexin V-FITC and TUNEL stain. Additionally, the tumoricidal effect of pyrogallol was measured using a xenograft nude mice model. After 5 weeks of pyrogallol treatment could cause the regression of tumor. Taken in vitro and in vivo studies together, these results suggest that pyrogallol can be developed as a promising anti-lung cancer drug particular for the non-small cell lung cancer (NSCLC).
Yang
Chih-Jen
CJ
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Wang
Chuan-Sheng
CS
Hung
Jen-Yu
JY
Huang
Hurng-Wern
HW
Chia
Yi-Chen
YC
Wang
Pei-Hui
PH
Weng
Ching-Feng
CF
Huang
Ming-Shyan
MS
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000494:pharmacology; D004195:Disease Models, Animal; D016195:G2 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D011748:Pyrogallol / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D003603:Cytotoxins; D006131:Growth Inhibitors; D011748:Pyrogallol