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[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

박승우|송시영|방승민|박윤정|Jing Wen
연세대학교의과대학 (Yonsei University College of Medicine)|2006.10|Yonsei Medical Journal|제47권 제5호|pp. 688-697

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참고문헌

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초록

[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild- type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53- expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53- expressing cells by inducing temporal growth arrest.

Abstract

[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild- type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53- expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53- expressing cells by inducing temporal growth arrest.

참고문헌 (38)

  1. "Green tea constituent epigallocatechin- 3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells", 89, pp.1881~1886 (1997)
  2. "Effects of the tyrosine protein kinase inhibitor genistein on the proliferation, activation of cultured rat hepatic stellate cells", 8, pp.739~745 (2002)
  3. "Tangeretin induces cell-cycle G1 arrest through inhibiting Cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells", 23, pp.1677~1684 (2002)
  4. "Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents", 60, pp.1051~1059 (2000)
  5. "Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells", 39, pp.292~299 (2001)
  6. "Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances", 428, pp.305~327 (1999)
  7. "Chemoprotective properties of some pungent ingredients present in red pepper and ginger", 402, pp.259~267 (1998)
  8. "Keishi-ka-kei-to, a traditional Chinese herbal medicine, inhibits pulmonary metastasis of B16 melanoma", 17, pp.873~878 (1997)
  9. -gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice, , 1998, 139~144
  10. "Modifying effects of fungal and herb metabolites on azoxymethane-induced intestinal carcinogenesis in rats", pp.1273~8
  11. -gingerol, , 2001, 850~853
  12. -paradol, , 1998, 163~168
  13. "Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of Helicobacter pylori", 23, pp.3699~3702 (2003)
  14. "Chemoradiotherapy for pancreatic cancer : current status and perspectives", 9, pp.451~457 (2004)
  15. "Current options for palliative treatment in patients with pancreatic cancer", 19, pp.63~75 (2001)
  16. "p53 expression affects the efficacy of adjuvant chemotherapy after resection of invasive ductal carcinoma of the pancreas", 18, pp.3773~3779 (1998)
  17. "Role of p53 and p16 gene alterations in determining response to concurrent paclitaxel and radiation in solid tumor", 9, pp.4~11 (1999)
  18. "Overexpression of Bax sensitizes human pancreatic cancer cells to apoptosis induced by chemotherapeutic agents", 49, pp.504~510 (2002)
  19. "K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on Cyclin B1", Cdc2 kinase activity, G2, pp.2000, 2[DOI]
  20. "Clinical implications of p53 mutations", 55, pp.64~75 (1999)
  21. "Expression of p21 WAF1", Cip1 in the p53-dependent pathway is related to prognosis in patients with advanced esophageal carcinoma, 1999, pp.5, 2445~2449
  22. "Involvement of PI3K", Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy, 2003, pp.17, 590~603
  23. -Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF- kappaB in phorbol ester-stimulated mouse skin, , 2005, 2558~2567
  24. "Inhibition of carcinogenesis by dietary polyphenolic compounds", 21, pp.381~406 (2001)
  25. "Overexpression of mouse D-type Cyclins accelerates G1 phase in rodent fibroblasts", pp.1559~71
  26. "Cyclin D1 is an essential mediator of apoptotic neuronal cell death", 15, pp.46~54 (1996)
  27. "The promise and obstacle of p53 as a cancer therapeutic agent", 2, pp.329~345 (2002)
  28. "the DNA template alterations that trigger p53-dependent DNA damage response pathways" (1815)
  29. "p53, the cellular gatekeeper for growth and division", 88, pp.323~331 (1997)
  30. "The tumor suppressor gene TP53: implications for cancer management and therpay", 41, pp.551~583 (2004)
  31. "CDK inhibitors: positive and negative regulators of G1-phase progression", 13, pp.1501~1512 (1999)
  32. "Ras promotes p21(Waf1", Cip1) protein stability via a Cyclin D1- imposed block in proteasome-mediated degradation, 2003, pp.22, 2036~2046
  33. "Signals from Ras and Rho GTPases interact to regulate expression of p21Waf1", Cip1, 1998, pp.394, 295~299
  34. "Growth factor-dependent induction of p21(CIP1) by the green tea polyphenol, epigallocatechin gallate", 154, pp.151~161 (2000)
  35. "Apoptotic signaling pathways: caspases and stress-activated protein kinases", 35, pp.24~27 (2002)
  36. "Cellular survival: a play in three Akts", 13, pp.2905~2927 (1999)
  37. "Targeting serine", threonine protein kinase B, pp.2002, 2[DOI]
  38. "AKT plays a central role in tumorigenesis", 98, pp.10983~10985 (2001)

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