Cucurbitacin I inhibits cell migration and invasion and enhances chemosensitivity in colon cancer

Song,Junmin; Liu,Hongxiang; Li,Zhen; Yang,Chao; Wang,Chaojie

doi:10.3892/or.2015.3749

Cucurbitacin I inhibits cell migration and invasion and enhances chemosensitivity in colon cancer

Authors:
- Junmin Song
- Hongxiang Liu
- Zhen Li
- Chao Yang
- Chaojie Wang
View Affiliations

Affiliations: Department of General Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China, Department of Oncology, Henan Provincial People's Hospital, Zhengzhou 450003, P.R. China
Published online on: January 26, 2015 https://doi.org/10.3892/or.2015.3749
Pages: 1867-1871

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colorectal cancers are the third most common types of cancers worldwide. Surgical resection is unable to eliminate tumors completely due to metastasis. A demand for new chemotherapeutic tools exists. In the present study, we examined the chemopreventive potential of cucurbitacin I, a natural component extracted from plants of the Cucurbitaceae family, in the colon cancer cell line COLO205. We hypothesized that cucurbitacin I would prevent colon cancer cell migration and invasion, and sensitize colon cancer cells to chemotherapy. Our data demonstrated that exposure of the COLO205 cells to cucurbitacin I significantly decreased cell viability. Furthermore our data demonstrated for the first time that in the COLO205 cells, cucurbitacin I could suppress the cell migration and invasion, and harbor chemosensitization activity against colon cancer. The anticancer activity of cucurbitacin I was accomplished by downregulating p-STAT3 and MMP-9 expression. Collectively, our results suggest that cucurbitacin I may be a potent adjuvant chemotherapeutic agent for colon cancer with anti-migration, anti-invasion and chemosensitizing activities.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
2	Cunningham D, Atkin W, Lenz HJ, et al: Colorectal cancer. Lancet. 375:1030–1047. 2010. View Article : Google Scholar : PubMed/NCBI
3	Labianca R, Beretta GD, Kildani B, et al: Colon cancer. Crit Rev Oncol Hematol. 74:106–133. 2010. View Article : Google Scholar : PubMed/NCBI
4	Pihl E, Hughes ES, McDermott FT, Milne BJ and Price AB: Disease-free survival and recurrence after resection of colorectal carcinoma. J Surg Oncol. 16:333–341. 1981. View Article : Google Scholar : PubMed/NCBI
5	Cresanta JL: Epidemiology of cancer in the United States. Prim Care. 19:419–441. 1992.PubMed/NCBI
6	Greenwald P: Colon cancer overview. Cancer. 70(Suppl 5): S1206–S1215. 1992. View Article : Google Scholar
7	Zhang H, Qian Y, Liu Y, et al: Celastrus orbiculatus extract induces mitochondrial-mediated apoptosis in human hepatocellular carcinoma cells. J Tradit Chin Med. 32:621–626. 2012. View Article : Google Scholar
8	Liu J and Liu Y: Influence of Erbanxiao solution on inhibiting angiogenesis in stasis toxin stagnation of non-small cell lung cancer. J Tradit Chin Med. 33:303–306. 2013. View Article : Google Scholar : PubMed/NCBI
9	Kang J, Lee N, Ahn Y and Lee H: Study on improving blood flow with Korean red ginseng substances using digital infrared thermal imaging and Doppler sonography: randomized, double blind, placebo-controlled clinical trial with parallel design. J Tradit Chin Med. 33:39–45. 2013. View Article : Google Scholar : PubMed/NCBI
10	Surh YJ: Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol. 40:1091–1097. 2002. View Article : Google Scholar : PubMed/NCBI
11	Su Y, Li G, Zhang X, et al: JSI-124 inhibits glioblastoma multiforme cell proliferation through G2/M cell cycle arrest and apoptosis augment. Cancer Biol Ther. 7:1243–1249. 2008. View Article : Google Scholar : PubMed/NCBI
12	van Kester MS, Out-Luiting JJ, von dem Borne PA, Willemze R, Tensen CP and Vermeer MH: Cucurbitacin I inhibits Stat3 and induces apoptosis in Sézary cells. J Invest Dermatol. 128:1691–1695. 2008. View Article : Google Scholar : PubMed/NCBI
13	Blaskovich MA, Sun J, Cantor A, Turkson J, Jove R and Sebti SM: Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res. 63:1270–1279. 2003.PubMed/NCBI
14	Chen JC, Chiu MH, Nie RL, Cordell GA and Qiu SX: Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep. 22:386–399. 2005. View Article : Google Scholar : PubMed/NCBI
15	Chen CL, Hsieh FC, Lieblein JC, et al: Stat3 activation in human endometrial and cervical cancers. Br J Cancer. 96:591–599. 2007. View Article : Google Scholar : PubMed/NCBI
16	Lo HW, Cao X, Zhu H and Ali-Osman F: Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clin Cancer Res. 14:6042–6054. 2008. View Article : Google Scholar : PubMed/NCBI
17	Kim HJ, Park JH and Kim JK: Cucurbitacin-I, a natural cell-permeable triterpenoid isolated from Cucurbitaceae, exerts potent anticancer effect in colon cancer. Chem Biol Interact. 219:1–8. 2014. View Article : Google Scholar : PubMed/NCBI
18	Gu L, Feng J, Xu H, Luo M and Su D: Polyphyllin I inhibits proliferation and metastasis of ovarian cancer cell line HO-8910PM in vitro. J Tradit Chin Med. 33:325–333. 2013. View Article : Google Scholar : PubMed/NCBI
19	Luo XS, Wu XW and Gu Q: An experimental study of a modified Dahuang Zhechong pill on the - angiogenesis of RF/6A cells in vitro. J Tradit Chin Med. 32:75–81. 2012. View Article : Google Scholar : PubMed/NCBI
20	Lui VW, Boehm AL, Koppikar P, et al: Antiproliferative mechanisms of a transcription factor decoy targeting signal transducer and activator of transcription (STAT) 3: the role of STAT1. Mol Pharmacol. 71:1435–1443. 2007. View Article : Google Scholar : PubMed/NCBI
21	Hsu HS, Huang PI, Chang YL, et al: Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer-derived CD133-positive cells. Cancer. 117:2970–2985. 2011. View Article : Google Scholar : PubMed/NCBI
22	Chen YW, Chen KH, Huang PI, et al: Cucurbitacin I suppressed stem-like property and enhanced radiation-induced apoptosis in head and neck squamous carcinoma-derived CD44⁺ALDH1⁺ cells. Mol Cancer Ther. 9:2879–2892. 2010. View Article : Google Scholar : PubMed/NCBI
23	Alghasham AA: Cucurbitacins - a promising target for cancer therapy. Int J Health Sci. 7:77–89. 2013. View Article : Google Scholar
24	Ren Y, Yu K, Sun S, et al: JSI124 inhibits breast cancer cell growth by suppressing the function of B cells via the downregulation of signal transducer and activator of transcription 3. Oncol Lett. 8:928–932. 2014.PubMed/NCBI
25	Ishdorj G, Johnston JB and Gibson SB: Inhibition of constitutive activation of STAT3 by curcurbitacin-I (JSI-124) sensitized human B-leukemia cells to apoptosis. Mol Cancer Ther. 9:3302–3314. 2010. View Article : Google Scholar : PubMed/NCBI
26	Björklund M and Koivunen E: Gelatinase-mediated migration and invasion of cancer cells. Biochim Biophys Acta. 1755:37–69. 2005.PubMed/NCBI
27	Li X, Yang G, Li X, et al: Traditional Chinese medicine in cancer care: a review of controlled clinical studies published in Chinese. PLoS One. 8:e603382013. View Article : Google Scholar : PubMed/NCBI
28	Knecht DA, LaFleur RA, Kahsai AW, Argueta CE, Beshir AB and Fenteany G: Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. PLoS One. 5:e140392010. View Article : Google Scholar : PubMed/NCBI
29	Maloney KN, Fujita M, Eggert US, et al: Actin-aggregating cucurbitacins from Physocarpus capitatus. J Nat Prod. 71:1927–1929. 2008. View Article : Google Scholar : PubMed/NCBI
30	Abdulghani J, Gu L, Dagvadorj A, et al: Stat3 promotes metastatic progression of prostate cancer. Am J Pathol. 172:1717–1728. 2008. View Article : Google Scholar : PubMed/NCBI
31	Deng JY, Sun D, Liu XY, Pan Y and Liang H: STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer. World J Gastroenterol. 16:5380–5387. 2010. View Article : Google Scholar : PubMed/NCBI
32	Dauer DJ, Ferraro B, Song L, et al: Stat3 regulates genes common to both wound healing and cancer. Oncogene. 24:3397–3408. 2005. View Article : Google Scholar : PubMed/NCBI
33	Xie TX, Huang FJ, Aldape KD, et al: Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res. 66:3188–3196. 2006. View Article : Google Scholar : PubMed/NCBI
34	Li WC, Ye SL, Sun RX, et al: Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res. 12:7140–7148. 2006. View Article : Google Scholar : PubMed/NCBI
35	Silver DL, Naora H, Liu J, Cheng W and Montell DJ: Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res. 64:3550–3558. 2004. View Article : Google Scholar : PubMed/NCBI
36	Horiguchi A, Oya M, Shimada T, Uchida A, Marumo K and Murai M: Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J Urol. 168:762–765. 2002. View Article : Google Scholar : PubMed/NCBI
37	Kusaba T, Nakayama T, Yamazumi K, et al: Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors. J Clin Pathol. 58:833–838. 2005. View Article : Google Scholar : PubMed/NCBI
38	Ihle JN: The Stat family in cytokine signaling. Curr Opin Cell Biol. 13:211–217. 2001. View Article : Google Scholar : PubMed/NCBI
39	Levy DE and Darnell JE Jr: Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 3:651–662. 2002. View Article : Google Scholar : PubMed/NCBI
40	Chang CJ, Chiang CH, Song WS, et al: Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells. Childs Nerv Syst. 28:363–373. 2012. View Article : Google Scholar : PubMed/NCBI