The antibacterial peptide from Bombyx mori cecropinXJ induced growth arrest and apoptosis in human hepatocellular carcinoma cells

Xia,Lijie; Wu,Yanling; Ma,Ji; Yang,Jianhua; Zhang,Fuchun

doi:10.3892/ol.2016.4601

The antibacterial peptide from Bombyx mori cecropinXJ induced growth arrest and apoptosis in human hepatocellular carcinoma cells

Authors:
- Lijie Xia
- Yanling Wu
- Ji Ma
- Jianhua Yang
- Fuchun Zhang
View Affiliations

Affiliations: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China, Department of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Texas, TX 77030, USA
Published online on: May 17, 2016 https://doi.org/10.3892/ol.2016.4601
Pages: 57-62
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

CecropinXJ is a cationic antimicrobial peptide originally isolated from the larvae of Bombyx mori. The anticancer effect of cecropinXJ has been reported in various tumor cells, including leukemia, gastric and esophageal cancer cells. However, the activity of cecropinXJ on hepatocellular carcinoma (HCC) and its underlying mechanism have not been investigated to date. Therefore, the present study investigated the efficacy and associated mechanism of cecropinXJ in Huh‑7 cells. Flow cytometric analysis was performed to determine the presence of cell cycle arrested and apoptotic cells. CecropinXJ significantly inhibited the growth of Huh‑7 cells in a dose‑ and time‑dependent manner. CecropinXJ treatment for 24 h induced S cell cycle arrest and apoptosis, in addition to loss of the mitochondrial membrane potential, in hepatoma cells. CecropinXJ induced HCC cell apoptosis by activating caspase-3 and poly(ADP-ribose) polymerase. Furthermore, cecropinXJ downregulated the expression of B‑cell lymphoma 2 (Bcl‑2), while upregulated the expression of Bcl‑2‑associated death promoter and Bcl‑2‑associated X protein. In conclusion, the results of the present study suggest that cecropinXJ may be an active anti-HCC agent and provide novel insights into the mechanism of cecropinXJ.

View Figures

View References

1	Somboon K, Siramolpiwat S and Vilaichone RK: Epidemiology and survival of hepatocellular carcinoma in the central region of Thailand. Asian Pac J Cancer Prev. 15:3567–3570. 2014. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L and He J: The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 32:106–112. 2013. View Article : Google Scholar : PubMed/NCBI
3	Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar : PubMed/NCBI
4	Zolfagharzadeh F and Roshan VD: Pretreatment hepatoprotective effect of regular aerobic training against hepatic toxicity induced by doxorubicin in rats. Asian Pac J Cancer Prev. 14:2931–2936. 2013. View Article : Google Scholar : PubMed/NCBI
5	Sostelly A, Henin E, Chauvenet L, Hardy-Bessard AC, Jestin-Le Tallec V, Kirsher S, Leyronnas C, Ligeza-Poisson C, Ramdane S, Salavt J, et al: Can we predict chemo-induced hematotoxicity in elderly patients treated with pegylated liposomal doxorubicin? Results of a population-based model derived from the DOGMES phase II trial of the GINECO. J Geriatr Oncol. 4:48–57. 2013. View Article : Google Scholar : PubMed/NCBI
6	Cruciani RA, Barker JL, Zasloff M, Chen HC and Colamonici O: Antibiotic magainins exert cytolytic activity against transformed cell lines through channel formation. Proc Natl Acad Sci USA. 88:3792–3796. 1991. View Article : Google Scholar : PubMed/NCBI
7	Jin XB, Li XB, Zhu JY, Lu XM, Shen J, Chu FJ and Mei HF: The target of Musca domestica cecropin on human hepatocellular carcinoma BEL-7402 cells. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 29:271–273. 2011.(In Chinese). PubMed/NCBI
8	Jin XB, Wang YJ, Liang LL, Pu QH, Shen J, Lu XM, Chu FJ and Zhu JY: Cecropin suppresses human hepatocellular carcinoma BEL-7402 cell growth and survival in vivo without side-toxicity. Asian Pac J Cancer Prev. 15:5433–5436. 2014. View Article : Google Scholar : PubMed/NCBI
9	Boman HG, Nilsson-Faye I, Paul K and Rasmuson T: Insect immunity. I. Characteristics of an inducible cell-free antibacterial reaction in hemolymph of Samia cynthia pupae. Infect Immun. 10:136–145. 1974.PubMed/NCBI
10	Steiner H, Hultmark D, Engström A, Bennich H and Boman HG: Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature. 292:246–248. 1981. View Article : Google Scholar : PubMed/NCBI
11	Suttmann H, Retz M, Paulsen F, Harder J, Zwergel U, Kamradt J, Wullich B, Unteregger G, Stöckle M and Lehmann J: Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells. BMC Urol. 8:52008. View Article : Google Scholar : PubMed/NCBI
12	Jin X, Mei H, Li X, Ma Y, Zeng AH, Wang Y, Lu X, Chu F, Wu Q and Zhu J: Apoptosis-inducing activity of the antimicrobial peptide cecropin of Musca domestica in human hepatocellular carcinoma cell line BEL-7402 and the possible mechanism. Acta Biochim Biophys Sin (Shanghai). 42:259–265. 2010. View Article : Google Scholar : PubMed/NCBI
13	Pan WR, Chen PW, Chen YL, Hsu HC, Lin CC and Chen WJ: Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage. J Dairy Sci. 96:7511–7520. 2013. View Article : Google Scholar : PubMed/NCBI
14	Lin WJ, Chien YL, Pan CY, Lin TL, Chen JY, Chiu SJ and Hui CF: Epinecidin-1, an antimicrobial peptide from fish (Epinephelus coioides) which has an antitumor effect like lytic peptides in human fibrosarcoma cells. Peptides. 30:283–290. 2009. View Article : Google Scholar : PubMed/NCBI
15	Hui L, Leung K and Chen HM: The combined effects of antibacterial peptide cecropin A and anti-cancer agents on leukemia cells. Anticancer Res. 22:2811–2816. 2002.PubMed/NCBI
16	Yeaman MR and Yount NY: Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 55:27–55. 2003. View Article : Google Scholar : PubMed/NCBI
17	Chou HT, Wen HW, Kuo TY, Lin CC and Chen WJ: Interaction of cationic antimicrobial peptides with phospholipid vesicles and their antibacterial activity. Peptides. 31:1811–1820. 2010. View Article : Google Scholar : PubMed/NCBI
18	Chen HM, Wang W, Smith D and Chan SC: Effects of the anti-bacterial peptide cecropin B and its analogs, cecropins B1 and B2, on liposomes, bacteria, and cancer cells. Biochim Biophys Acta. 1336:171–179. 1997. View Article : Google Scholar : PubMed/NCBI
19	Cerón JM, Contreras-Moreno J, Puertollano E, de Cienfuegos GÁ, Puertollano MA and de Pablo MA: The antimicrobial peptide cecropin A induces caspase-independent cell death in human promyelocytic leukemia cells. Peptides. 31:1494–1503. 2010. View Article : Google Scholar : PubMed/NCBI
20	Li JY, Zhang FC and Ma ZH: Prokaryotic expression of cecropin gene isolated from the silkworm Bombyx mori Xinjiang race and antibacterial activity of fusion cecropin. Acta Entomologica Sinica. 47:407–411. 2004.(In Chinese).
21	Xia L, Liu Z, Ma J, Sun S, Yang J and Zhang F: Expression, purification and characterization of cecropin antibacterial peptide from Bombyx mori in Saccharomyces cerevisiae. Protein Expr Purif. 90:47–54. 2013. View Article : Google Scholar : PubMed/NCBI
22	Xia L, Zhang F, Liu Z, Ma J and Yang J: Expression and characterization of cecropinXJ, a bioactive antimicrobial peptide from Bombyx mori (Bombycidae, Lepidoptera) in Escherichia coli. Exp Ther Med. 5:1745–1751. 2013.PubMed/NCBI
23	Xia L, Wu Y, Kang S, Ma J, Yang J and Zhang F: CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells. Acta Biochim Biophys Sin (Shanghai). 46:867–876. 2014. View Article : Google Scholar : PubMed/NCBI
24	Cerón JM, Contreras-Moreno J, Puertollano E, de Cienfuegos GÁ, Puertollano MA and de Pablo MA: The antimicrobial peptide cecropin A induces caspase-independent cell death in human promyelocytic leukemia cells. Peptides. 31:1494–1503. 2010. View Article : Google Scholar : PubMed/NCBI
25	Kuwana T and Newmeyer DD: Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol. 15:691–699. 2003. View Article : Google Scholar : PubMed/NCBI
26	Chen YL, Li JH, Yu CY, Lin CJ, Chiu PH, Chen PW, Lin CC and Chen WJ: Novel cationic antimicrobial peptide GW-H1 induced caspase-dependent apoptosis of hepatocellular carcinoma cell lines. Peptides. 36:257–265. 2012. View Article : Google Scholar : PubMed/NCBI
27	Huh JE, Kang JW, Nam D, Baek YH, Choi DY, Park DS and Lee JD: Melittin suppresses VEGF-A-induced tumor growth by blocking VEGFR-2 and the COX-2-mediated MAPK signaling pathway. J Nat Prod. 75:1922–1929. 2012. View Article : Google Scholar : PubMed/NCBI
28	Papo N and Shai Y: Host defense peptides as new weapons in cancer treatment. Cell Mol Life Sci. 62:784–790. 2005. View Article : Google Scholar : PubMed/NCBI
29	Moore AJ, Devine DA and Bibby MC: Preliminary experimental anticancer activity of cecropins. Pept Res. 7:265–269. 1994.PubMed/NCBI
30	Chernysh S, Kim SI, Bekker G, Pleskach VA, Filatova NA, Anikin VB, Platonov VG and Bulet P: Antiviral and antitumor peptides from insects. Proc Natl Acad Sci USA. 99:12628–12632. 2002. View Article : Google Scholar : PubMed/NCBI
31	Li B, Gu W, Zhang C, Huang XQ, Han KQ and Ling CQ: Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Onkologie. 29:367–371. 2006.PubMed/NCBI
32	Ohtake T, Fujimoto Y, Ikuta K, Saito H, Ohhira M, Ono M and Kohgo Y: Proline-rich antimicrobial peptide, PR-39 gene transduction altered invasive activity and actin structure in human hepatocellular carcinoma cells. Br J Cancer. 81:393–403. 1999. View Article : Google Scholar : PubMed/NCBI
33	Thornberry NA and Lazebnik Y: Caspases: Enemies within. Science. 281:1312–1316. 1998. View Article : Google Scholar : PubMed/NCBI
34	Liu X, Kim CN, Yang J, Jemmerson R and Wang X: Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell. 86:147–157. 1996. View Article : Google Scholar : PubMed/NCBI
35	Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP and Wang X: Prevention of apoptosis by Bcl-2: Release of cytochrome c from mitochondria blocked. Science. 275:1129–1132. 1997. View Article : Google Scholar : PubMed/NCBI