The Synergistic Apoptotic Interaction of Panaxadiol and Epigallocatechin Gallate in Human Colorectal Cancer Cells

Panaxadiol (PD) is a purified sapogenin of ginseng saponins, which exhibits anticancer activity. Epigallocatechin gallate (EGCG), a major catechin in green tea, is a strong botanical antioxidant. In this study, we investigated the possible synergistic anticancer effects of PD and EGCG on human colorectal cancer cells and explored the potential role of apoptosis in the synergistic activities. Effects of selected compounds on HCT‐116 and SW‐480 human colorectal cancer cells were evaluated by a modified trichrome stain cell proliferation analysis. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with PI/RNase or annexin V/PI. Cell growth was suppressed after treatment with PD (10 and 20 µm) for 48 h. When PD (10 and 20 µm) was combined with EGCG (10, 20, and 30 µm), significantly enhanced antiproliferative effects were observed in both cell lines. Combining 20 µm of PD with 20 and 30 µm of EGCG significantly decreased S‐phase fractions of cells. In the apoptotic assay, the combination of PD and EGCG significantly increased the percentage of apoptotic cells compared with PD alone (p < 0.01). The synergistic apoptotic effects were also supported by docking analysis, which demonstrated that PD and EGCG bound in two different sites of the annexin V protein. Data from this study suggested that apoptosis might play an important role in the EGCG‐enhanced antiproliferative effects of PD on human colorectal cancer cells. Copyright © 2012 John Wiley & Sons, Ltd.

[1]  S. Shankar,et al.  Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. , 2011, Biochemical pharmacology.

[2]  Lian‐Wen Qi,et al.  Red notoginseng: higher ginsenoside content and stronger anticancer potential than Asian and American ginseng. , 2011, Food chemistry.

[3]  Lian-Wen Qi,et al.  Isolation and analysis of ginseng: advances and challenges. , 2011, Natural product reports.

[4]  Chong-Zhi Wang,et al.  Synthesis of protopanaxadiol derivatives and evaluation of their anticancer activities , 2011, Anti-cancer drugs.

[5]  Lian‐Wen Qi,et al.  American ginseng: potential structure-function relationship in cancer chemoprevention. , 2010, Biochemical pharmacology.

[6]  A. Jemal,et al.  Cancer Statistics, 2010 , 2010, CA: a cancer journal for clinicians.

[7]  J. Lambert,et al.  The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. , 2010, Archives of biochemistry and biophysics.

[8]  T. He,et al.  Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells. , 2010, Cancer letters.

[9]  Xin Wang,et al.  Cancer prevention by tea: animal studies, molecular mechanisms and human relevance , 2009, Nature Reviews Cancer.

[10]  D. Newman,et al.  Impact of natural products on developing new anti-cancer agents. , 2009, Chemical reviews.

[11]  Chong-Zhi Wang,et al.  The mitochondrial pathway is involved in American ginseng-induced apoptosis of SW-480 colon cancer cells. , 2009, Oncology reports.

[12]  Kwang-tae Choi,et al.  Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer , 2008, Acta Pharmacologica Sinica.

[13]  Ping Chen,et al.  Combined chemotherapy of hydroxycampothecin with oxaliplatin as an adjuvant treatment for human colorectal cancer. , 2008, The Tohoku journal of experimental medicine.

[14]  C. Reutelingsperger,et al.  Extracellular annexin A5: functions of phosphatidylserine-binding and two-dimensional crystallization. , 2008, Biochimica et biophysica acta.

[15]  T. He,et al.  Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots. , 2007, Planta medica.

[16]  T. He,et al.  Steamed American ginseng berry: ginsenoside analyses and anticancer activities. , 2006, Journal of agricultural and food chemistry.

[17]  Reyes Artacho,et al.  Beneficial Effects of Green Tea—A Review , 2006, Journal of the American College of Nutrition.

[18]  Keisuke Ito,et al.  Green Tea Component, Catechin, Induces Apoptosis of Human Malignant B Cells via Production of Reactive Oxygen Species , 2005, Clinical Cancer Research.

[19]  P. Trouvé,et al.  Externalization of endogenous annexin A5 participates in apoptosis of rat cardiomyocytes. , 2004, Cardiovascular research.

[20]  S. Helms Cancer prevention and therapeutics: Panax ginseng. , 2004, Alternative medicine review : a journal of clinical therapeutic.

[21]  J. Benz,et al.  Annexins: from structure to function. , 1997, Biological chemistry.

[22]  L. Hartwell,et al.  Checkpoints: controls that ensure the order of cell cycle events. , 1989, Science.

[23]  Hyo Il Jang,et al.  Wild Panax ginseng (Panax ginseng C.A. Meyer) protects against methotrexate-induced cell regression by enhancing the immune response in RAW 264.7 macrophages. , 2010, The American journal of Chinese medicine.

[24]  Chong-Zhi Wang,et al.  Letter to the editor: Panaxadiol's anticancer activity is enhanced by epicatechin. , 2010, The American journal of Chinese medicine.

[25]  Z. Cao,et al.  Long-term effects of Panax ginseng on disposition of fexofenadine in rats in vivo. , 2009, The American journal of Chinese medicine.

[26]  H. Park,et al.  (-)-Epigallocatechin-3-gallate (EGCG) increases the viability of serum-starved A549 cells through its effect on Akt. , 2009, The American journal of Chinese medicine.

[27]  H. Nagawa,et al.  Epigallocatechin gallate induces apoptosis of monocytes. , 2005, The Journal of allergy and clinical immunology.

[28]  H. Nomoto,et al.  Cancer prevention by natural compounds. , 2004, Drug metabolism and pharmacokinetics.