β-lapachone suppresses the proliferation of human malignant melanoma cells by targeting specificity protein 1

Bang,Woong; Jeon,Young-Joo; Cho,Jin  Hyoung; Lee,Ra  Ham; Park,Seon-Min; Shin,Jae-Cheon; Choi,Nag-Jin; Choi,Yung  Hyun; Cho,Jung-Jae; Seo,Jae-Min; Lee,Seung-Yeop; Shim,Jung-Hyun; Chae,Jung-Il

doi:10.3892/or.2015.4439

β-lapachone suppresses the proliferation of human malignant melanoma cells by targeting specificity protein 1

Authors:
- Woong Bang
- Young-Joo Jeon
- Jin Hyoung Cho
- Ra Ham Lee
- Seon-Min Park
- Jae-Cheon Shin
- Nag-Jin Choi
- Yung Hyun Choi
- Jung-Jae Cho
- Jae-Min Seo
- Seung-Yeop Lee
- Jung-Hyun Shim
- Jung-Il Chae
View Affiliations

Affiliations: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 561-756, Republic of Korea, Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea, Department of Animal Science, College of Agricultural and Life Science, Chonbuk National University, Jeonju 561‑756, Republic of Korea, Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea, Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea, Department of Prosthodontics, School of Dentistry and Institute of Oral Bio-Science and Research Institute of Clinical Medicine, Chonbuk National University, Jeonju 561-756, Republic of Korea, Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea
Published online on: November 20, 2015 https://doi.org/10.3892/or.2015.4439
Pages: 1109-1116

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

β-lapachone (β-lap), a novel natural quinone derived from the bark of the Pink trumpet tree (Tabebuia avellanedae) has been demonstrated to have anticancer activity. In this study, we investigated whether β-lap exhibits anti-proliferative effects on two human malignant melanoma (HMM) cell lines, G361 and SK-MEL-28. The effects of β-lap on the HMM cell lines were investigated using 3-(4,5-dimethylthiazol-2-yl)‑5-(3-carboxymethoxyphenyl)‑2-(4-sulfophenyl-2H-tetrazolium (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V and Dead cell assay, mitochondrial membrane potential (MMP) assay and western blot analysis. We demonstrated that β-lap significantly induced apoptosis and suppressed cell viability in the HMM cells. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly downregulated by β-lap in a dose- and time-dependent manner. Furthermore, β-lap modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and apoptosis-associated proteins. Taken together, our findings indicated that β-lap modulates Sp1 transactivation and induces apoptotic cell death through the regulation of cell cycle- and apoptosis-associated proteins. Thus, β-lap may be used as a promising anticancer drug for cancer prevention and may improve the clinical outcome of patients with cancer.

View Figures

View References

1	Bandarchi B, Ma L, Navab R, Seth A and Rasty G: From melanocyte to metastatic malignant melanoma. Dermatol Res Pract. 2010:5837482010.PubMed/NCBI
2	Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D and Bray F: Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 49:1374–1403. 2013. View Article : Google Scholar : PubMed/NCBI
3	Erdmann F, Lortet-Tieulent J, Schüz J, Zeeb H, Greinert R, Breitbart EW and Bray F: International trends in the incidence of malignant melanoma 1953–2008 - are recent generations at higher or lower risk? Int J Cancer. 132:385–400. 2013. View Article : Google Scholar
4	Kesmodel SB and Spitz FR: Gene therapy for cancer and metastatic disease. Expert Rev Mol Med. 5:1–18. 2003. View Article : Google Scholar : PubMed/NCBI
5	Bhatia S, Tykodi SS and Thompson JA: Treatment of metastatic melanoma: An overview. Oncology (Williston Park). 23:488–496. 2009.
6	Moon DO, Kang CH, Kim MO, Jeon YJ, Lee JD, Choi YH and Kim GY: Beta-lapachone (LAPA) decreases cell viability and telomerase activity in leukemia cells: Suppression of telomerase activity by LAPA. J Med Food. 13:481–488. 2010. View Article : Google Scholar : PubMed/NCBI
7	Guiraud P, Steiman R, Campos-Takaki GM, Seigle-Murandi F and Simeon de Buochberg M: Comparison of antibacterial and antifungal activities of lapachol and beta-lapachone. Planta Med. 60:373–374. 1994. View Article : Google Scholar : PubMed/NCBI
8	de Almeida ER, da Silva Filho AA, dos Santos ER and Lopes CA: Antiinflammatory action of lapachol. J Ethnopharmacol. 29:239–241. 1990. View Article : Google Scholar : PubMed/NCBI
9	Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS and Pardee AB: Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. Proc Natl Acad Sci USA. 90:1839–1842. 1993. View Article : Google Scholar : PubMed/NCBI
10	Planchon SM, Wuerzberger S, Frydman B, Witiak DT, Hutson P, Church DR, Wilding G and Boothman DA: Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: A p53-independent response. Cancer Res. 55:3706–3711. 1995.PubMed/NCBI
11	Planchon SM, Pink JJ, Tagliarino C, Bornmann WG, Varnes ME and Boothman DA: Beta-lapachone-induced apoptosis in human prostate cancer cells: Involvement of NQO1/xip3. Exp Cell Res. 267:95–106. 2001. View Article : Google Scholar : PubMed/NCBI
12	Müller K, Sellmer A and Wiegrebe W: Potential antipsoriatic agents: Lapacho compounds as potent inhibitors of HaCaT cell growth. J Nat Prod. 62:1134–1136. 1999. View Article : Google Scholar : PubMed/NCBI
13	Sitônio MM, Carvalho Júnior CH, Campos IA, Silva JB, Lima MC, Góes AJ, Maia MB, Rolim Neto PJ and Silva TG: Anti-inflammatory and anti-arthritic activities of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (β-lapachone). Inflamm Res. 62:107–113. 2013. View Article : Google Scholar
14	Frydman B, Marton LJ, Sun JS, Neder K, Witiak DT, Liu AA, Wang HM, Mao Y, Wu HY, Sanders MM, et al: Induction of DNA topoisomerase II-mediated DNA cleavage by beta-lapachone and related naphthoquinones. Cancer Res. 57:620–627. 1997.PubMed/NCBI
15	Chau YP, Shiah SG, Don MJ and Kuo ML: Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone-induced apoptosis and differentiation in human leukemia cells. Free Radic Biol Med. 24:660–670. 1998. View Article : Google Scholar : PubMed/NCBI
16	Shiah SG, Chuang SE, Chau YP, Shen SC and Kuo ML: Activation of c-Jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation-dependent pathway. Cancer Res. 59:391–398. 1999.PubMed/NCBI
17	Choi YH, Kang HS and Yoo MA: Suppression of human prostate cancer cell growth by beta-lapachone via down-regulation of pRB phosphorylation and induction of Cdk inhibitor p21(WAF1/CIP1). J Biochem Mol Biol. 36:223–229. 2003. View Article : Google Scholar : PubMed/NCBI
18	Pink JJ, Wuerzberger-Davis S, Tagliarino C, Planchon SM, Yang X, Froelich CJ and Boothman DA: Activation of a cysteine protease in MCF-7 and T47D breast cancer cells during beta-lapachone-mediated apoptosis. Exp Cell Res. 255:144–155. 2000. View Article : Google Scholar : PubMed/NCBI
19	Wuerzberger SM, Pink JJ, Planchon SM, Byers KL, Bornmann WG and Boothman DA: Induction of apoptosis in MCF-7:WS8 breast cancer cells by beta-lapachone. Cancer Res. 58:1876–1885. 1998.PubMed/NCBI
20	Dong GZ, Oh ET, Lee H, Park MT, Song CW and Park HJ: Beta-lapachone suppresses radiation-induced activation of nuclear factor-kappaB. Exp Mol Med. 42:327–334. 2010. View Article : Google Scholar : PubMed/NCBI
21	Yu HY, Kim SO, Jin CY, Kim GY, Kim WJ, Yoo YH and Choi YH: β-lapachone-induced apoptosis of human gastric carcinoma AGS cells is caspase-dependent and regulated by the PI3K/Akt pathway. Biomol Ther (Seoul). 22:184–192. 2014. View Article : Google Scholar
22	Wierstra I: Sp1: Emerging roles - beyond constitutive activation of TATA-less housekeeping genes. Biochem Biophys Res Commun. 372:1–13. 2008. View Article : Google Scholar : PubMed/NCBI
23	Black AR, Black JD and Azizkhan-Clifford J: Sp1 and krüppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol. 188:143–160. 2001. View Article : Google Scholar : PubMed/NCBI
24	Kong LM, Liao CG, Fei F, Guo X, Xing JL and Chen ZN: Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci. 101:1463–1470. 2010. View Article : Google Scholar : PubMed/NCBI
25	Sankpal UT, Goodison S, Abdelrahim M and Basha R: Targeting Sp1 transcription factors in prostate cancer therapy. Med Chem. 7:518–525. 2011. View Article : Google Scholar : PubMed/NCBI
26	Jiang Y, Wang L, Gong W, Wei D, Le X, Yao J, Ajani J, Abbruzzese JL, Huang S and Xie K: A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer. Clin Exp Metastasis. 21:755–764. 2004. View Article : Google Scholar
27	Kim DW, Ko SM, Jeon YJ, Noh YW, Choi NJ, Cho SD, Moon HS, Cho YS, Shin JC, Park SM, et al: Anti-proliferative effect of honokiol in oral squamous cancer through the regulation of specificity protein 1. Int J Oncol. 43:1103–1110. 2013.PubMed/NCBI
28	Zhang R, Luo H, Wang S, Chen W, Chen Z, Wang HW, Chen Y, Yang J, Zhang X, Wu W, et al: MicroRNA-377 inhibited proliferation and invasion of human glioblastoma cells by directly targeting specificity protein 1. Neuro Oncol. 16:1510–1522. 2014. View Article : Google Scholar : PubMed/NCBI
29	Abdelrahim M, Smith R III, Burghardt R and Safe S: Role of Sp proteins in regulation of vascular endothelial growth factor expression and proliferation of pancreatic cancer cells. Cancer Res. 64:6740–6749. 2004. View Article : Google Scholar : PubMed/NCBI
30	Shin JA, Han G, Kim HJ, Kim HM and Cho SD: Chemopreventive and chemotherapeutic effect of a novel histone deacetylase inhibitor, by specificity protein 1 in MDA-MB-231 human breast cancer cells. Eur J Cancer Prev. 23:277–285. 2014. View Article : Google Scholar : PubMed/NCBI
31	Cho JH, Shin JC, Cho JJ, Choi YH, Shim JH and Chae JI: Esculetin (6,7-dihydroxycoumarin): A potential cancer chemo-preventive agent through suppression of Sp1 in oral squamous cancer cells. Int J Oncol. 46:265–271. 2015.
32	Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P and Longo VD: Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). 1:988–1007. 2009.
33	Wilson RM and Danishefsky SJ: Small molecule natural products in the discovery of therapeutic agents: The synthesis connection. J Org Chem. 71:8329–8351. 2006. View Article : Google Scholar : PubMed/NCBI
34	Tobin DD, Menon M, Menon M, Spatta BC, Hodges EV and Perry DG: The intrapsychics of gender: A model of self-socialization. Psychol Rev. 117:601–622. 2010. View Article : Google Scholar : PubMed/NCBI
35	Li CJ, Averboukh L and Pardee AB: Beta-lapachone, a novel DNA topoisomerase I inhibitor with a mode of action different from camptothecin. J Biol Chem. 268:22463–22468. 1993.PubMed/NCBI
36	Jackson JK, Higo T, Hunter WL and Burt HM: Topoisomerase inhibitors as anti-arthritic agents. Inflamm Res. 57:126–134. 2008. View Article : Google Scholar : PubMed/NCBI
37	Tudan C, Jackson JK, Higo TT and Burt HM: The effect of inhibiting topoisomerase I and II on the anti-apoptotic response associated with pro-inflammatory crystals of calcium pyrophosphate dihydrate in human neutrophils. Inflamm Res. 52:8–17. 2003. View Article : Google Scholar : PubMed/NCBI
38	Safe S and Abdelrahim M: Sp transcription factor family and its role in cancer. Eur J Cancer. 41:2438–2448. 2005. View Article : Google Scholar : PubMed/NCBI
39	Li L and Davie JR: The role of Sp1 and Sp3 in normal and cancer cell biology. Ann Anat. 192:275–283. 2010. View Article : Google Scholar : PubMed/NCBI
40	Hsu TI, Wang MC, Chen SY, Yeh YM, Su WC, Chang WC and Hung JJ: Sp1 expression regulates lung tumor progression. Oncogene. 31:3973–3988. 2012. View Article : Google Scholar :
41	Kavurma MM and Khachigian LM: Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells by repressing p21^WAF1/Cip1 transcription and cyclin D1-Cdk4-p21^WAF1/Cip1 complex formation. J Biol Chem. 278:32537–32543. 2003. View Article : Google Scholar : PubMed/NCBI
42	Xu R, Zhang P, Huang J, Ge S, Lu J and Qian G: Sp1 and Sp3 regulate basal transcription of the survivin gene. Biochem Biophys Res Commun. 356:286–292. 2007. View Article : Google Scholar : PubMed/NCBI
43	Chae JI, Jeon YJ and Shim JH: Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells. Oncol Rep. 29:2318–2324. 2013.PubMed/NCBI
44	Hong IK, Byun HJ, Lee J, Jin YJ, Wang SJ, Jeoung DI, Kim YM and Lee H: The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways. J Biol Chem. 289:15691–15704. 2014. View Article : Google Scholar : PubMed/NCBI
45	Liu X, Yang WT and Zheng PS: Msi1 promotes tumor growth and cell proliferation by targeting cell cycle checkpoint proteins p21, p27 and p53 in cervical carcinomas. Oncotarget. 5:10870–10885. 2014. View Article : Google Scholar : PubMed/NCBI
46	Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI
47	Murray AW: Recycling the cell cycle: Cyclins revisited. Cell. 116:221–234. 2004. View Article : Google Scholar : PubMed/NCBI
48	Ewen ME and Lamb J: The activities of cyclin D1 that drive tumorigenesis. Trends Mol Med. 10:158–162. 2004. View Article : Google Scholar : PubMed/NCBI
49	Weinstein IB: Relevance of cyclin D1 and other molecular markers to cancer chemoprevention. J Cell Biochem Suppl. 25:23–28. 1996. View Article : Google Scholar : PubMed/NCBI
50	Fu M, Wang C, Li Z, Sakamaki T and Pestell RG: Minireview: Cyclin D1: normal and abnormal functions. Endocrinology. 145:5439–5447. 2004. View Article : Google Scholar : PubMed/NCBI
51	Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC and Altieri DC: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 396:580–584. 1998. View Article : Google Scholar : PubMed/NCBI
52	Jarrin M, Mansergh FC, Boulton ME, Gunhaga L and Wride MA: Survivin expression is associated with lens epithelial cell proliferation and fiber cell differentiation. Mol Vis. 18:2758–2769. 2012.PubMed/NCBI
53	Xu Q, Liu M, Xu N and Zhu H: Variation in Sp1 binding sites correlates with expression of survivin in breast cancer. Mol Med Rep. 10:1395–1399. 2014.PubMed/NCBI
54	Grütter MG: Caspases: Key players in programmed cell death. Curr Opin Struct Biol. 10:649–655. 2000. View Article : Google Scholar : PubMed/NCBI
55	Porter AG and Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6:99–104. 1999. View Article : Google Scholar : PubMed/NCBI
56	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
57	Vaziri H, West MD, Allsopp RC, Davison TS, Wu YS, Arrowsmith CH, Poirier GG and Benchimol S: ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J. 16:6018–6033. 1997. View Article : Google Scholar : PubMed/NCBI
58	Zauli G, Gibellini D, Caputo A, Bassini A, Negrini M, Monne M, Mazzoni M and Capitani S: The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2 gene expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells. Blood. 86:3823–3834. 1995.PubMed/NCBI
59	Yang E, Zha J, Jockel J, Boise LH, Thompson CB and Korsmeyer SJ: Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 80:285–291. 1995. View Article : Google Scholar : PubMed/NCBI