Abstract
Docetaxel, a member of the taxane family, has been shown to induce apoptosis in a variety of cancer cells. However, toxicity at therapeutic doses has precluded the use of docetaxel alone for the management of cancer patients. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. Our previous study showed that PSK induced downregulation of several invasion-related factors, suggesting an interaction of PSK with transcriptional factors. In this study, we showed that PSK dose dependently enhanced apoptosis induced by 1 nM of docetaxel in a human pancreatic cancer cell line NOR-P1. Furthermore, PSK inhibited docetaxel-induced nuclear factor kappa B (NF-κB) activation. Moreover, the expression of cellular inhibitor of apoptosis protein (cIAP-1), which is transcriptionally regulated by NF-κB and functions as an antiapoptotic molecule through interrupting the caspase pathway, was also inhibited by treatment with PSK plus docetaxel. As a result, PSK enhanced the docetaxel-induced caspase-3 activation. In addition, treatment by transfection of NF-κB decoy oligodeoxynucleotides (ODNs), but not scramble ones, inhibited the expression of cIAP-1 in NOR-P1 cells and induced a significant increase in docetaxel-induced apoptosis. Our data indicate that PSK suppresses the docetaxel-induced NF-κB activation pathway. Combination of PSK with a low dose of docetaxel may be a new therapeutic strategy to treat patients with pancreatic cancer.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Anai H, Sakaguchi Y, Emi Y, Kohnoe S, Maehara Y and, Sugimachi K . (1991). Anticancer Drugs, 2, 275–278.
Aota K, Azuma M, Yamashita T, Tamatani T, Motegi K, Ishimaru N, Hayashi Y and Sato M . (2000). Biochem. Biophys. Res. Commun., 273, 1168–1174.
Arlt A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE and Schafer H . (2001). Oncogene, 20, 859–868.
Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W, Royer HD, Grinstein E, Greiner A, Scheidereit C and Dorken B . (1997). J. Clin. Invest., 100, 2961–2969.
Bissery MC, Nohynek G, Sanderink GJ and Lavelle F . (1995). Anticancer Drugs, 6, 339–355.
Cascinu S, Gasparini G, Catalano V, Silva RR, Pancera G, Morabito A, Giordani P, Gattuso D and Catalano G . (1999). Ann. Oncol., 10, 1377–1379.
Chu ZL, Mckinsey TA, Liu L, Gentry JJ, Malim MH and Ballard DW . (1997). Pro. Natl. Acad. Sci. USA, 94, 10057–10062.
Cortes JE and Pazdur R . (1995). J. Clin. Oncol., 13, 2643–2655.
Cui X, Imaizumi T, Yoshida H, Tanji K, Matsumiya T and Satoh K . (2000). Biochim. Biophys. Acta, 1524, 178–182.
Ebina T and Murata K . (1992). Jpn. J. Cancer Res., 83, 775–782.
Fisher M and Yang LX . (2002). Anticancer Res., 22, 1737–1754.
Fukushima M . (1996). Semin. Oncol., 23, 369–378.
Haldar S, Basu A and Croce CM . (1997). Cancer Res., 57, 229–233.
Huang Y, Johnson KR, Norris JS and Fan W . (2000). Cancer Res., 60, 4426–4432.
Iino Y, Takai Y, Sugamata N and Morishita Y . (1992). Anticancer Res., 12, 2101–2103.
Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y and Ueno K . (1996). Biol. Pharm. Bull., 19, 1518–1520.
Iwaguchi T, Shimizu M and Hayashi H . (1989). J. Biochem. Biophys. Methods, 18, 157–166.
Kaye SB . (1995). Semin. Oncol., 22, 30–33.
Kojima M, Morisaki T, Izuhara K, Uchiyama A, Matsunari Y, Katano M and Tanaka M . (2000). Oncogene, 19, 1225–1231.
Kolfschoten GM, Hulscher TM, Duyndam MC, Pinedo HM and Boven E . (2002). Biochem. Pharmacol., 63, 733–743.
Lenzi R, Yalcin S, Evans DB and Abbruzzese JL . (2002). Cancer Invest., 20, 464–472.
Mori H, Mihara M, Teshima K, Uesugi U, Xu Q, Sakamoto O and Koda A . (1987). Int. J. Immunopharmacol., 9, 881–892.
Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C . (1991). J. Immunol. Methods, 139, 271–279.
Okada S, Sakata Y, Matsuno S, Kurihara M, Sasaki Y, Ohashi Y and Taguchi T . (1999). Br. J. Cancer, 80, 438–443.
Rougier P, Adenis A, Ducreux M, de Forni M, Bonneterre J, Dembak M, Clouet P, Lebecq A, Baille P, Lefresne-Soulas F, Blanc C and Armand JP . (2000). Eur. J. Cancer, 36, 1016–1025.
Rowinsky EK . (1997). Annu. Rev. Med., 48, 353–374.
Roy N, Deveraux QL, Takahashi R, Salvesen GS and Reed JC . (1997). EMBO J., 16, 6914–6925.
Sato N, Mizumoto K, Beppu K, Maehara N, Kusumoto M, Nabae T, Morisaki T, Katano N and Tanaka M . (2000). Cancer Lett., 155, 153–161.
Shibata M, Nezu T, Kanou H, Nagata Y, Kimura T, Takekawa M, Anclo K and Fukuzawa M . (2002). Cancer Invest., 20, 166–173.
Spencer W, Kwon H, Crepieux P, Leclerc N, Lin R and Hiscott J . (1999). Oncogene, 18, 495–505.
Stathopoulos GP, Mavroudis D, Tsavaris N, Kouroussis C, Aravantinos G, Agelaki S, Kakolyris S, Rigatos SK, Karabekios S and Georgoulias V . (2000). Ann. Oncol., 12, 101–103.
Takahashi Y and Mai M . (2001). Gan To Kagaku Ryoho, 28, 531–534.
Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K and Orita K . (1984). Cancer Treat. Rev., 11, 131–155.
Vos IH, Govers R, Grone HJ, Kleij L, Schurink M, De Weger RA, Goldschmeding R and Rabelink TJ . (2000). FASEB. J., 14, 815–822.
Wang CY, Mayo MW, Korneluk RG, Goeddel DV and Baldwin Jr AS . (1998). Science, 281, 1680–1683.
Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR and Chiao PJ . (1999). Clin. Cancer Res., 5, 119–127.
Wright ME, Han DK and Hockenbery DM . (2000). FEBS Lett., 481, 13–18.
Zhang H, Morisaki T, Matsunaga H, Sato N, Uchiyama A, Hashizume K, Nagumo F, Tadano J and Katano M . (2000). Clin. Exp. Metast., 18, 343–352.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, H., Morisaki, T., Nakahara, C. et al. PSK-mediated NF-κB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Oncogene 22, 2088–2096 (2003). https://doi.org/10.1038/sj.onc.1206310
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1206310
Keywords
This article is cited by
-
Herb–drug interactions between the medicinal mushrooms Lingzhi and Yunzhi and cytotoxic anticancer drugs: a systematic review
Chinese Medicine (2020)
-
Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives
Surgery Today (2012)
-
NF-κB activation enhances cell death by antimitotic drugs in human prostate cancer cells
Molecular Cancer (2010)
-
Inhibition of NF-κB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel
Archives of Pharmacal Research (2009)
-
The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis
BMC Cancer (2008)