doi:10.1016/j.biocel.2006.06.002
Copyright © 2006 Elsevier Ltd All rights reserved.
External Qi of Yan Xin Qigong differentially regulates the Akt and extracellular signal-regulated kinase pathways and is cytotoxic to cancer cells but not to normal cells
Xin Yana, b, , , Hua Shenb, Hongjian Jiangc, Chengsheng Zhangd, Dan Hud, Jun Wangb and Xinqi Wue
aInstitute of Chongqing Traditional Chinese Medicine, Chongqing, PR China
bNew Medical Science Research Institute, New York, NY 10107, USA
cMassachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
dDana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
eChildren's Hospital, Harvard Medical School, Boston, MA 02115, USA
Received 14 February 2006; revised 21 May 2006; accepted 2 June 2006. Available online 27 June 2006.
Abstract
Long-term clinical observations and ongoing studies have shown significant antitumor effect of external Qi of Yan Xin Qigong which originated from traditional Chinese medicine. In order to understand the molecular and cellular mechanisms underlying the antitumor effect of external Qi of Yan Xin Qigong, we have examined its cytotoxic effect on BxPC3 pancreatic cancer cells and its effect on the Akt and extracellular signal-regulated kinase pathways. We found that external Qi of Yan Xin Qigong dramatically inhibited basal phosphorylation levels of Akt and extracellular signal-regulated kinases, epidermal growth factor-mediated phosphorylation of extracellular signal-regulated kinases, and phosphatidylinositol 3-kinase activity. External Qi of Yan Xin Qigong also inhibited constitutive and inducible activities of nuclear factor-kappa B, a target of the Akt and epidermal growth factor receptor pathways. Furthermore, a single 5 min exposure of BxPC3 cells to external Qi of Yan Xin Qigong induced apoptosis, accompanied by a dramatic increase of the sub-G1 cell population, DNA fragmentation, and cleavage of caspases 3, 8 and 9, and poly(ADP-ribose) polymerase. Prolonged treatment with external Qi of Yan Xin Qigong caused rapid lysis of BxPC3 cells. In contrast, treatment of fibroblasts with external Qi of Yan Xin Qigong induced transient activation of extracellular signal-regulated kinases and Akt, and caused no cytotoxic effect. These findings suggest that external Qi of Yan Xin Qigong may differentially regulate these survival pathways in cancer versus normal cells and exert cytotoxic effects preferentially on cancer cells, and that it could potentially be a valuable approach for therapy of pancreatic carcinomas.
Keywords: Akt; ERK1/2; External Qi; Yan Xin Qigong; Pancreatic cancer
Abbreviations: EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; EMSA, electrophoresis mobility shift assay; ERK, extracellular signal-regulated kinase; FBS, fetal bovine serum; IkB, inhibitor of NF-κB; IKK, IκB kinase; LDH, lactic dehydrogenase; MTS, [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; inner salt]; NF-κB, nuclear factor-kappa B; PARP, poly(ADP-ribose) polymerase; PI, propidium iodide; PI3K, phosphatidylinositol 3-kinase; PMSF, phenylmethylsulfonyl fluoride; TCM, traditional Chinese medicine; TLC, thin layer chromatography; TNF-α, tumor necrotic factor α; YXQ, Yan Xin Qigong
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