Bioactive proanthocyanidins inhibit growth and induce apoptosis in human melanoma cells by decreasing the accumulation of β-catenin

Vaid,Mudit; Singh,Tripti; Prasad,Ram; Katiyar,Santosh  K.

doi:10.3892/ijo.2015.3286

Bioactive proanthocyanidins inhibit growth and induce apoptosis in human melanoma cells by decreasing the accumulation of β-catenin

Authors:
- Mudit Vaid
- Tripti Singh
- Ram Prasad
- Santosh K. Katiyar
View Affiliations

Affiliations: Department of Dermatology, University of Alabama at Birmingham, AL 35294, USA
Published online on: December 10, 2015 https://doi.org/10.3892/ijo.2015.3286
Pages: 624-634

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

Melanoma is a highly aggressive form of skin cancer with poor survival rate. Aberrant activation of Wnt/β-catenin has been observed in nearly one-third of human melanoma cases thereby indicating that targeting Wnt/β-catenin signaling could be a promising strategy against melanoma development. In the present study, we determined chemotherapeutic effect of grape seed proanthocyanidins (GSPs) on the growth of melanoma cells and validated their protective effects in vivo using a xenograft mouse model, and assessed if β-catenin is the target of GSP chemotherapeutic effect. Our in vitro data show that treatment of A375 and Hs294t human melanoma cells with GSPs inhibit the growth of melanoma cells, which was associated with the reduction in the levels of β-catenin. Administration of dietary GSPs (0.2 and 0.5%, w/w) in supplementation with AIN76A control diet significantly inhibited the growth of melanoma tumor xenografts in nude mice. Furthermore, dietary GSPs inhibited the xenograft growth of Mel928 (β-catenin-activated), while did not inhibit the xenograft growth of Mel1011 (β-catenin-inactivated) cells. These observations were further verified by siRNA knockdown of β-catenin and forced overexpression of β-catenin in melanoma cells using a cell culture model.

View Figures

View References

1	Hall HI, Miller DR, Rogers JD and Bewerse B: Update on the incidence and mortality from melanoma in the United States. J Am Acad Dermatol. 40:35–42. 1999. View Article : Google Scholar : PubMed/NCBI
2	Strouse JJ, Fears TR, Tucker MA and Wayne AS: Pediatric melanoma: Risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol. 23:4735–4741. 2005. View Article : Google Scholar : PubMed/NCBI
3	Mittal A, Elmets CA and Katiyar SK: Dietary feeding of proanthocyanidins from grape seeds prevents photocarcinogenesis in SKH-1 hairless mice: Relationship to decreased fat and lipid peroxidation. Carcinogenesis. 24:1379–1388. 2003. View Article : Google Scholar : PubMed/NCBI
4	Sharma SD, Meeran SM and Katiyar SK: Dietary grape seed proanthocyanidins inhibit UVB-induced oxidative stress and activation of mitogen-activated protein kinases and nuclear factor-kappaB signaling in in vivo SKH-1 hairless mice. Mol Cancer Ther. 6:995–1005. 2007. View Article : Google Scholar : PubMed/NCBI
5	Nandakumar V, Singh T and Katiyar SK: Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett. 269:378–387. 2008. View Article : Google Scholar : PubMed/NCBI
6	Vaid M, Singh T and Katiyar SK: Grape seed proanthocyanidins inhibit melanoma cell invasiveness by reduction of PGE2 synthesis and reversal of epithelial-to-mesenchymal transition. PLoS One. 6:e215392011. View Article : Google Scholar : PubMed/NCBI
7	Sun Q, Prasad R, Rosenthal E and Katiyar SK: Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition. BMC Complement Altern Med. 11:134–145. 2011. View Article : Google Scholar : PubMed/NCBI
8	Meeran SM, Vaid M, Punathil T and Katiyar SK: Dietary grape seed proanthocyanidins inhibit 12-O-tetradecanoyl phorbol-13-acetate-caused skin tumor promotion in 7,12-dimethylbenz[a] anthracene-initiated mouse skin, which is associated with the inhibition of inflammatory responses. Carcinogenesis. 30:520–528. 2009. View Article : Google Scholar : PubMed/NCBI
9	Akhtar S, Meeran SM, Katiyar N and Katiyar SK: Grape seed proanthocyanidins inhibit the growth of human non-small cell lung cancer xenografts by targeting insulin-like growth factor binding protein-3, tumor cell proliferation, and angiogenic factors. Clin Cancer Res. 15:821–831. 2009. View Article : Google Scholar : PubMed/NCBI
10	Prasad R, Vaid M and Katiyar SK: Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway. PLoS One. 7:e430642012. View Article : Google Scholar : PubMed/NCBI
11	Prasad R and Katiyar SK: Bioactive phytochemical proanthocyanidins inhibit growth of head and neck squamous cell carcinoma cells by targeting multiple signaling molecules. PLoS One. 7:e464042012. View Article : Google Scholar : PubMed/NCBI
12	Sinnberg T, Menzel M, Kaesler S, Biedermann T, Sauer B, Nahnsen S, Schwarz M, Garbe C and Schittek B: Suppression of casein kinase 1alpha in melanoma cells induces a switch in beta-catenin signaling to promote metastasis. Cancer Res. 70:6999–7009. 2010. View Article : Google Scholar : PubMed/NCBI
13	Syed DN, Afaq F, Maddodi N, Johnson JJ, Sarfaraz S, Ahmad A, Setaluri V and Mukhtar H: Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels. J Invest Dermatol. 131:1291–1299. 2011. View Article : Google Scholar : PubMed/NCBI
14	Lucero OM, Dawson DW, Moon RT and Chien AJ: A re-evaluation of the ‘oncogenic’ nature of Wnt/beta-catenin signaling in melanoma and other cancers. Curr Oncol Rep. 12:314–318. 2010. View Article : Google Scholar : PubMed/NCBI
15	Delmas V, Beermann F, Martinozzi S, Carreira S, Ackermann J, Kumasaka M, Denat L, Goodall J, Luciani F, Viros A, et al: Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev. 21:2923–2935. 2007. View Article : Google Scholar : PubMed/NCBI
16	Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL and Moon RT: Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc Natl Acad Sci USA. 106:1193–1198. 2009. View Article : Google Scholar : PubMed/NCBI
17	Maelandsmo GM, Holm R, Nesland JM, Fodstad Ø and Flørenes VA: Reduced beta-catenin expression in the cytoplasm of advanced-stage superficial spreading malignant melanoma. Clin Cancer Res. 9:3383–3388. 2003.PubMed/NCBI
18	Kageshita T, Hamby CV, Ishihara T, Matsumoto K, Saida T and Ono T: Loss of beta-catenin expression associated with disease progression in malignant melanoma. Br J Dermatol. 145:210–216. 2001. View Article : Google Scholar : PubMed/NCBI
19	Bachmann IM, Straume O, Puntervoll HE, Kalvenes MB and Akslen LA: Importance of P-cadherin, beta-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma. Clin Cancer Res. 11:8606–8614. 2005. View Article : Google Scholar : PubMed/NCBI
20	Mantena SK, Sharma SD and Katiyar SK: Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP. Carcinogenesis. 27:2018–2027. 2006. View Article : Google Scholar : PubMed/NCBI
21	Vaid M, Sharma SD and Katiyar SK: Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: Development of topical formulation. Carcinogenesis. 31:2004–2011. 2010. View Article : Google Scholar : PubMed/NCBI
22	Adams JM and Cory S: Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 26:61–66. 2001. View Article : Google Scholar : PubMed/NCBI
23	Chao DT and Korsmeyer SJ: BCL-2 family: Regulators of cell death. Annu Rev Immunol. 16:395–419. 1998. View Article : Google Scholar : PubMed/NCBI
24	Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X and He X: Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 108:837–847. 2002. View Article : Google Scholar : PubMed/NCBI
25	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI
26	Hockenbery D, Nuñez G, Milliman C, Schreiber RD and Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 348:334–336. 1990. View Article : Google Scholar : PubMed/NCBI
27	Klaus A and Birchmeier W: Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 8:387–398. 2008. View Article : Google Scholar : PubMed/NCBI
28	Gavert N and Ben-Ze'ev A: β-Catenin signaling in biological control and cancer. J Cell Biochem. 102:820–828. 2007. View Article : Google Scholar : PubMed/NCBI
29	Rimm DL, Caca K, Hu G, Harrison FB and Fearon ER: Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma. Am J Pathol. 154:325–329. 1999. View Article : Google Scholar : PubMed/NCBI
30	Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science. 275:1790–1792. 1997. View Article : Google Scholar : PubMed/NCBI
31	Demunter A, Libbrecht L, Degreef H, De Wolf-Peeters C and van den Oord JJ: Loss of membranous expression of beta-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by exon 3 mutations. Mod Pathol. 15:454–461. 2002. View Article : Google Scholar : PubMed/NCBI
32	Lowy AM, Clements WM, Bishop J, Kong L, Bonney T, Sisco K, Aronow B, Fenoglio-Preiser C and Groden J: β-Catenin/Wnt signaling regulates expression of the membrane type 3 matrix metalloproteinase in gastric cancer. Cancer Res. 66:4734–4741. 2006. View Article : Google Scholar : PubMed/NCBI
33	Li YJ, Wei ZM, Meng YX and Ji XR: Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: Relationships with carcinogenesis and metastasis. World J Gastroenterol. 11:2117–2123. 2005. View Article : Google Scholar : PubMed/NCBI
34	Qi J, Chen N, Wang J and Siu CH: Transendothelial migration of melanoma cells involves N-cadherin-mediated adhesion and activation of the beta-catenin signaling pathway. Mol Biol Cell. 16:4386–4397. 2005. View Article : Google Scholar : PubMed/NCBI