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Article Open Access

Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles

Corrigendum in: /10.3892/ijo.2018.4584
  • Authors:
    • George Mattheolabakis
    • Ruixue Wang
    • Basil Rigas
    • Gerardo G. Mackenzie
  • View Affiliations / Copyright

    Affiliations: Department of Medicine, Stony Brook University, Stony Brook, NY 11794-8175, USA, Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY 11794-8175, USA
    Copyright: © Mattheolabakis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1035-1044
    |
    Published online on: August 25, 2017
       https://doi.org/10.3892/ijo.2017.4103
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Abstract

Pancreatic cancer (PC) is one of the most difficult cancers to treat. Since the current chemotherapy is inadequate and various biological approaches have failed, the need for agents that have a potential to treat PC is pressing. Phospho-valproic acid (P-V), a novel anticancer agent, is efficacious in xenograft models of human PC and is apparently safe. In the present study, we evaluated whether formulating P-V in nanoparticles could enhance its anticancer efficacy. In a mouse model of Kras/pancreatitis-associated PC, P-V, orally administered, inhibited the incidence of acinar-to-ductal metaplasia by 60%. To improve its efficacy, we formulated P-V in five different polymeric nanoparticles. Poly-(L)-lactic acid- poly(ethylene glycol) (PLLA-PEG) nanoparticles proved the optimal formulation. PLLA-PEG improved P-V's pharmacokinetics in mice enhancing the levels of P-V in blood. Compared to control, P-V formulated in PLLA-PEG suppressed the growth of MIA PaCa-2 xenografts by 81%, whereas P-V alone reduced it by 51% (p<0.01). Furthermore, P-V formulated in PLLA-PEG inhibited acinar-to-ductal metaplasia in mice with activated Kras, reducing it by 87% (p<0.02). In both disease models, P-V suppressed STAT3 phosphorylation at the Ser727 and Tyr705 residues; STAT3 is the pivotal molecular target of P-V. In conclusion, P-V is a promising agent against PC, and its formulation in PLLA-PEG nanoparticles enhances its efficacy by improving its pharmacokinetics.
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1 

Siegel RL, Miller KD and Jemal A V1: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Huang L, Mackenzie GG, Sun Y, Ouyang N, Xie G, Vrankova K, Komninou D and Rigas B: Chemotherapeutic properties of phospho-nonsteroidal anti-inflammatory drugs, a new class of anticancer compounds. Cancer Res. 71:7617–7627. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Mackenzie GG, Bartels LE, Xie G, Papayannis I, Alston N, Vrankova K, Ouyang N and Rigas B: A novel Ras inhibitor (MDC-1016) reduces human pancreatic tumor growth in mice. Neoplasia. 15:1184–1195. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Mackenzie GG, Sun Y, Huang L, Xie G, Ouyang N, Gupta RC, Johnson F, Komninou D, Kopelovich L and Rigas B: Phospho-sulindac (OxT-328), a novel sulindac derivative, is safe and effective in colon cancer prevention in mice. Gastroenterology. 139:1320–1332. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Mackenzie GG, Huang L, Alston N, Ouyang N, Vrankova K, Mattheolabakis G, Constantinides PP and Rigas B: Targeting mitochondrial STAT3 with the novel phospho-valproic acid (MDC-1112) inhibits pancreatic cancer growth in mice. PLoS One. 8:e615322013. View Article : Google Scholar : PubMed/NCBI

6 

Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes CH, Levy DE, Settleman J, Engelman JA and Bardeesy N: STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res. 71:5020–5029. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Fukuda A, Wang SC, Morris JP IV, Folias AE, Liou A, Kim GE, Akira S, Boucher KM, Firpo MA, Mulvihill SJ, et al: Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell. 19:441–455. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, Yoshimura A, Reindl W, Sipos B, Akira S, et al: Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 19:456–469. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Scholz A, Heinze S, Detjen KM, Peters M, Welzel M, Hauff P, Schirner M, Wiedenmann B and Rosewicz S: Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology. 125:891–905. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Buettner R, Mora LB and Jove R: Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res. 8:945–954. 2002.PubMed/NCBI

11 

Sahu RP and Srivastava SK: The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. J Natl Cancer Inst. 101:176–193. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Mattheolabakis G, Rigas B and Constantinides PP: Nanodelivery strategies in cancer chemotherapy: Biological rationale and pharmaceutical perspectives. Nanomedicine (Lond). 7:1577–1590. 2012. View Article : Google Scholar

13 

Soppimath KS, Aminabhavi TM, Kulkarni AR and Rudzinski WE: Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 70:1–20. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Brigger I, Dubernet C and Couvreur P: Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 54:631–651. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Mattheolabakis G, Taoufik E, Haralambous S, Roberts ML and Avgoustakis K: In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles. Eur J Pharm Biopharm. 71:190–195. 2009. View Article : Google Scholar

16 

Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, Peng Z, Huang S, Xiong HQ, Abbruzzese JL, et al: Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene. 22:319–329. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Deer EL, González-Hernández J, Coursen JD, Shea JE, Ngatia J, Scaife CL, Firpo MA and Mulvihill SJ: Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 39:425–435. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Sun Y and Rigas B: The thioredoxin system mediates redox-induced cell death in human colon cancer cells: Implications for the mechanism of action of anticancer agents. Cancer Res. 68:8269–8277. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Mackenzie GG, Queisser N, Wolfson ML, Fraga CG, Adamo AM and Oteiza PI: Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells. Int J Cancer. 123:56–65. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Mattheolabakis G, Papayannis I, Yang J, Vaeth BM, Wang R, Bandovic J, Ouyang N, Rigas B and Mackenzie GG: Phospho-aspirin (MDC-22) prevents pancreatic carcinogenesis in mice. Cancer Prev Res. 9:624–634. 2016. View Article : Google Scholar

21 

Mackenzie GG, Ouyang N, Xie G, Vrankova K, Huang L, Sun Y, Komninou D, Kopelovich L and Rigas B: Phospho-sulindac (OxT-328) combined with difluoromethylornithine prevents colon cancer in mice. Cancer Prev Res (Phila). 4:1052–1060. 2011. View Article : Google Scholar

22 

Fogar P, Greco E, Basso D, Habeler W, Navaglia F, Zambon CF, Tormen D, Gallo N, Cecchetto A, Plebani M, et al: Suicide gene therapy with HSV-TK in pancreatic cancer has no effect in vivo in a mouse model. Eur J Surg Oncol. 29:721–730. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Freeman JW, Mattingly CA and Strodel WE: Increased tumorigenicity in the human pancreatic cell line MIA PaCa-2 is associated with an aberrant regulation of an IGF-1 autocrine loop and lack of expression of the TGF-beta type RII receptor. J Cell Physiol. 165:155–163. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Mattheolabakis G, Papayannis I, Yang J, Vaeth BM, Wang R, Bandovic J, Ouyang N, Rigas B and Mackenzie GG: Phospho-aspirin (MDC-22) prevents pancreatic carcinogenesis in mice. Cancer Prev Res (Phila). 9:624–634. 2016. View Article : Google Scholar

25 

Li J and Saif MW: Advancements in the management of pancreatic cancer. JOP. 10:109–117. 2009.PubMed/NCBI

26 

Morris JP IV, Wang SC and Hebrok M: KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 10:683–695. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Zhan C, Gu B, Xie C, Li J, Liu Y and Lu W: Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. J Control Release. 143:136–142. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Ahmed F, Pakunlu RI, Srinivas G, Brannan A, Bates F, Klein ML, Minko T and Discher DE: Shrinkage of a rapidly growing tumor by drug-loaded polymersomes: pH-triggered release through copolymer degradation. Mol Pharm. 3:340–350. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Kim SC, Kim DW, Shim YH, Bang JS, Oh HS, Wan Kim S and Seo MH: In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release. 72:191–202. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Baumgart S, Chen NM, Siveke JT, König A, Zhang JS, Singh SK, Wolf E, Bartkuhn M, Esposito I, Heßmann E, et al: Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D. Cancer Discov. 4:688–701. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Mattheolabakis G, Wang R, Rigas B and Mackenzie GG: Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584. Int J Oncol 51: 1035-1044, 2017.
APA
Mattheolabakis, G., Wang, R., Rigas, B., & Mackenzie, G.G. (2017). Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584. International Journal of Oncology, 51, 1035-1044. https://doi.org/10.3892/ijo.2017.4103
MLA
Mattheolabakis, G., Wang, R., Rigas, B., Mackenzie, G. G."Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584". International Journal of Oncology 51.4 (2017): 1035-1044.
Chicago
Mattheolabakis, G., Wang, R., Rigas, B., Mackenzie, G. G."Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584". International Journal of Oncology 51, no. 4 (2017): 1035-1044. https://doi.org/10.3892/ijo.2017.4103
Copy and paste a formatted citation
x
Spandidos Publications style
Mattheolabakis G, Wang R, Rigas B and Mackenzie GG: Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584. Int J Oncol 51: 1035-1044, 2017.
APA
Mattheolabakis, G., Wang, R., Rigas, B., & Mackenzie, G.G. (2017). Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584. International Journal of Oncology, 51, 1035-1044. https://doi.org/10.3892/ijo.2017.4103
MLA
Mattheolabakis, G., Wang, R., Rigas, B., Mackenzie, G. G."Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584". International Journal of Oncology 51.4 (2017): 1035-1044.
Chicago
Mattheolabakis, G., Wang, R., Rigas, B., Mackenzie, G. G."Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly(ethylene glycol) nanoparticles Corrigendum in /10.3892/ijo.2018.4584". International Journal of Oncology 51, no. 4 (2017): 1035-1044. https://doi.org/10.3892/ijo.2017.4103
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