The traditional Chinese medicinal formula BDL301 has been used to inhibit inflammation for hundreds of years. The development of colorectal cancer and chronic inflammation are closely related. In this study, we investigated whether BDL301 could inhibit tumor growth. We found that angiogenesis and tumor growth were both inhibited in vivo. In addition, apoptosis was induced and the signal transducer and activator of transcription-3 (STAT3) pathway were suppressed in the colorectal cancer cells in vitro and in vivo by BDL301. This study demonstrates that BDL301 exerted significant anticancer activity by inhibiting the STAT3 pathways and inducing apoptosis in colorectal cancer cells.
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References
1.
AggarwalB.B., SethiG., AhnK.S., SandurS.K., PandeyM.K., KunnumakkaraA.B., SungB., and IchikawaH. (2006). Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann N Y Acad Sci, 1091, 151–169.
2.
BaldwinA.S. (2001). Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest, 107, 241–246.
3.
BarnesP.J., and KarinM. (1997). Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med, 336, 1066–1071.
4.
BloodC.H., and ZetterB.R. (1990). Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim Biophys Acta, 1032, 89–118.
5.
CarmelietP., and JainR.K. (2000). Angiogenesis in cancer and other diseases. Nature, 407, 249–257.
6.
CuiX., JinY., HofsethA.B., PenaE., HabigerJ., ChumanevichA., PoudyalD., NagarkattiM., NagarkattiP.S., SinghU.P., and HofsethL.J. (2010). Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prev Res (Phila), 3, 549–559.
7.
D'amoreP.A., and ThompsonR.W. (1987). Mechanisms of angiogenesis. Annu Rev Physiol, 49, 453–464.
8.
GarciaR., BowmanT.L., NiuG., YuH., MintonS., Muro-CachoC.A., CoxC.E., FalconeR., FaircloughR., ParsonsS., LaudanoA., GazitA., LevitzkiA., KrakerA., and JoveR. (2001). Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene, 20, 2499–2513.
9.
GretenF.R., and KarinM. (2004). The IKK/NF-kappaB activation pathway—a target for prevention and treatment of cancer. Cancer Lett, 206, 193–199.
10.
GrivennikovS.I., GretenF.R., and KarinM. (2010). Immunity, inflammation, and cancer. Cell, 140, 883–899.
11.
HasanJ., ByersR., and JaysonG.C. (2002). Intra-tumoural microvessel density in human solid tumours. Br J Cancer, 86, 1566–1577.
12.
JeonK.I., XuX., AizawaT., LimJ.H., JonoH., KwonD.S., AbeJ., BerkB.C., LiJ.D., and YanC. (2010). Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci U S A, 107, 9795–9800.
13.
KarinM., and Ben-NeriahY. (2000). Phosphorylation meets ubiquitination: the control of NF-kappaB activity. Annu Rev Immunol, 18, 621–663.
14.
KarinM. (2008). The IkappaB kinase—a bridge between inflammation and cancer. Cell Res, 18, 334–342.
15.
KlampferL. (2011). Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets, 11, 451–464.
16.
KnupferH., and PreissR. (2010). Serum interleukin-6 levels in colorectal cancer patients–a summary of published results. Int J Colorectal Dis, 25, 135–140.
17.
KusabaT., NakayamaT., YamazumiK., YakataY., YoshizakiA., NagayasuT., and SekineI. (2005). Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors. J Clin Pathol, 58, 833–838.
18.
LassmannS., SchusterI., WalchA., GöbelH., JüttingU., MakowiecF., HoptU., and WernerM. (2007). STAT3 mRNA and protein expression in colorectal cancer: effects on STAT3-inducible targets linked to cell survival and proliferation. J Clin Pathol, 60, 173–179.
19.
LeekR.D., HarrisA.L., and LewisC.E. (1994). Cytokine networks in solid human tumors: regulation of angiogenesis. J Leukoc Biol, 56, 423–435.
20.
LiY.Y., WangH., ChenJ., ZhaoL., ZhangH., ChaiY.F., and ZhangG.Q. (2010). RRLC-TOF/MS in identification of constituents and metabolites of Radix Saposhnikoviae in rat plasma and urine. Academic Journal of Second Military Medical University, 31, 760–763.
21.
NiuG., TanJ., TurnerJ.G., BrabhamJ.G., BurdelyaL.G., CrucianB.E., Wall-ApeltH., ZhaoR.J., and YuH. (2000). Bing de ling, a Chinese herbal formula, stimulates multifaceted immunologic responses in mice. DNA Cell Biol, 19, 515–520.
22.
PandeyM.K., SungB., AhnK.S., and AggarwalB.B. (2009). Butein suppresses constitutive and inducible signal transducer and activator of transcription (STAT) 3 activation and STAT3-regulated gene products through the induction of a protein tyrosine phosphatase SHP-1. Mol Pharmacol, 75, 525–533.
23.
ParkJ.K., HongR., KimK.J., LeeT.B., and LimS.C. (2008). Significance of p-STAT3 expression in human colorectal adenocarcinoma. Oncol Rep, 20, 597–604.
24.
PendyalaS., NeffL.M., Suárez-FariñasM., and HoltP.R. (2011). Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis. Am J Clin Nutr, 93, 234–242.
25.
PortaC., RiboldiE., and SicaA. (2011). Mechanisms linking pathogens-associated inflammation and cancer. Cancer Lett, 305, 250–262.
26.
SunderkötterC., SteinbrinkK., GoebelerM., BhardwajR., and SorgC. (1994). Macrophages and angiogenesis. J Leukoc Biol, 55, 410–422.
27.
XuQ., BrabhamJ.G., ZhangS., MunsterP., FieldsK., ZhaoR.J., and YuH. (2005). Chinese herbal formula, Bing De Ling, enhances antitumor effects and ameliorates weight loss induced by 5-fluorouracil in the mouse CT26 tumor model. DNA Cell Biol, 24, 470–475.
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