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01-02-2015 | Brief Report

Chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96) DNA vaccine generates different anti-tumor effects against tumors expressing the E7 protein of human papillomavirus

Authors: Afshin Khavari, Azam Bolhassani, Fatemeh Alizadeh, S. Zahra Bathaie, Prabha Balaram, Elnaz Agi, Rouhollah Vahabpour

Published in: Archives of Virology | Issue 2/2015

Abstract

Saffron and its components have been suggested as promising candidates for cancer prevention. Carotenoids and monoterpene aldehydes are two potent ingredients of saffron. The goal of the current study was to investigate the anti-tumor effect of chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96) DNA vaccine against tumors expressing the E7 protein of human papillomavirus. The in vitro cytotoxic and apoptotic effects of aqueous saffron extract and its components were evaluated in malignant TC-1 and non-malignant COS-7 cell lines. Then, multimodality treatments using E7-NT (gp96) DNA vaccine combined with saffron extract and its ingredients as well as single-modality treatments were tested for their efficacy in inhibiting large and bulky tumor growth. Saffron and its components exerted a considerable anti-tumor effect through prevention of cell growth and stimulation of programmed cell death. Furthermore, 100 % of mice treated with crocin were tumor-free, in contrast to DNA vaccine alone (~66.7 %) and DNA + crocin (~33.3 %) indicating the high potency of crocin as a chemotherapeutic agent. Interestingly, the multimodality treatment using DNA vaccine along with picrocrocin augmented the anti-tumor effects of picrocrocin. Thus, the combination of DNA vaccine with saffron extract and crocin at certain concentrations did not potentiate protective and therapeutic effects compared to mono-therapies for the control of TC-1 tumors.

Chermahini SH, Majid FAA, Sarmidi MR, Taghizadeh E, Salehnezhad S (2010) Impact of saffron as an anti-cancer and anti-tumor herb. Afr J Pharm Pharmacol 4(11):834–840

Li N, Lin G, Kwan YW, Min ZD (1999) Simultaneous quantification of five major biologically active ingredients of saffron by high-performance liquid chromatography. J Chromatogr A 849:349–355PubMedCrossRef

Loskutov AV, Beninger CW, Hosfield GL, Sink KC (2000) Development of an improved procedure for extraction and quantitation of safranal in stigmas of Crocus sativus L. using high performance liquid chromatography. Food Chem 69:87–95CrossRef

Mousavi SZ, Bathaie SZ (2011) Historical uses of saffron: identifying potential new avenues for modern research. Avicenna J Phytomed 1(2):57–66

Nair SC, Kurumboor SK, Hasegawa JH (1995) Saffron chemoprevention in biology and medicine: a review. Cancer Biother 10(4):257–264PubMedCrossRef

Kwon HK, Hwang JS, So JS, Lee CG, Sahoo A, Ryu JH, Jeon WK, Ko BS, Im CR, Lee SH, Park ZY, Im SH (2010) Cinnamon extract induces tumor cell death through inhibition of NF-κB and AP1. BMC Cancer 10:392PubMedCentralPubMedCrossRef

Gerster H (1993) Anticarcinogenic effect of common carotenoids. Int J Nutr Res 63:92–121

Escribano J, Alonso GL, Coca-Prados M, Fernandez JA (1996) Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett 100:23–30PubMedCrossRef

Abdullaev FI (2002) Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med Maywood 227:20–25PubMed

10.

Tarantilis PA, Polissiou M, Manfait M (1994) Separation of picrocrocin, cis-trans-crocins and safranal of saffron using high-performance liquid chromatography with photodiode-array detection. J Chromatogr A 664:55–61PubMedCrossRef

11.

Tavakkol-Afshari J, Brook A, Mousavi SH (2008) Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem Toxicol 46:3443–3447PubMedCrossRef

12.

Bolhasani A, Bathaie SZ, Yavari I, Moosavi-Movahedi AA, Ghaffari M (2005) Separation and purification of some components of Iranian saffron. Asian J Chem 17(2):725–729

13.

Cornet S, Biard C, Moret Y (2007) Is there a role for antioxidant carotenoids in limiting self-harming immune response in invertebrates? Biol Lett 3(3):284–288PubMedCentralPubMedCrossRef

14.

Wiener D, Gong X, Marisiddaiah R, Rubin L (2010) Effects of carotenoids on differential expression of scavenger receptors and cytokines in human monocyte-derived macrophage subpopulations. J Immunol 184:98–109

15.

Bolhassani A, Khavari A, Bathaie SZ (2014) Saffron and natural carotenoids: biochemical activities and anti-tumor effects. BBA Rev Cancer 1845:20–30

16.

zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350PubMedCrossRef

17.

Roden RB, Ling M, Wu TC (2004) Vaccination to prevent and treat cervical cancer. Hum Pathol 35:971–982PubMedCrossRef

18.

Tseng CW, Hung CF, Alvarez RD, Trimble C, Huh WK, Kim D, Chuang CM, Lin CT, Tsai YC, He L, Monie A, Wu TC (2008) Pretreatment with cisplatin enhances E7-specific CD8+ T-cell mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res 14(10):3185–3192PubMedCentralPubMedCrossRef

19.

Weir GM, Liwski RS, Mansour M (2011) Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines. Cancers 3:3114–3142PubMedCentralPubMedCrossRef

20.

Kang TH, Lee JH, Song CK, Han HD, Shin BC, Pai SI (2007) Epigallocatechin-3-Gallate enhances CD8+ T cell-mediated antitumor immunity induced by DNA vaccination. Cancer Res 67(2):802–811PubMedCentralPubMedCrossRef

21.

Chuang CM, Monie A, Wu A, Hung CF (2009) Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects. J Biomed Sci 16(49):1–11

22.

Ji H, Chang EY, Lin KY, Kurman RJ, Pardoll DM, Wu TC (1998) Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein. Int J Cancer 78:41–45PubMedCrossRef

23.

Bolhassani A, Ghasemi N, Servis C, Taghikhani M, Rafati S (2009) The efficiency of a novel delivery system (PEI600-Tat) in development of potent DNA vaccine using HPV16 E7 as a model antigen. Drug Deliv 16(4):196–204PubMedCrossRef

24.

Bolhassani A, Javanzad Sh, Saleh T, Hashemi M, Aghasadeghi MR, Sadat SM (2014) Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases. Hum Vaccines Immunother 10(2):1–12CrossRef

25.

Mohit E, Bolhassani A, Zahedifard F, Seyed N, Eslamifar A, Taghikhani M, Samimi-Rad K, Rafati S (2013) Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections. Mol Immunol 53:149–160PubMedCrossRef

26.

Bolhassani A, Zahedifard F, Taslimi Y, Taghikhani M, Nahavandian B, Rafati S (2009) Antibody detection against HPV16E7 and Gp96 fragments as biomarkers in cervical cancer patients. Indian J Med Res 130(5):533–541PubMed

27.

Abdullaev FI, Espinosa J, Aguirre J (2004) Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 28:426–432PubMedCrossRef

28.

Salomi MJ, Nair SC, Panikkar KR (1991) Inhibitory effects of Nigella sativa and saffron (Crocus sativus L.) on chemical carcinogenesis in mice. Nutr Cancer 16:67–72PubMedCrossRef

29.

Abdullaev FI, Frenkel GD (1992) Effect of saffron on cell colony formation and cellular nucleic acid and protein synthesis. Biofactors 3:201–204PubMed

30.

Abdullaev FI, Frenkel GD (1992) The effect of saffron on intracellular DNA, RNA and protein synthesis in malignant and non-malignant human cells. Biofactors 4:43–45PubMed

31.

Samarghandian S, Tavakkol Afshari J, Davoodi S (2011) Suppression of pulmonary tumor promotion and induction of apoptosis by Crocus sativus L. extraction. Appl Biochem Biotechnol 164(2):238–247PubMedCrossRef

32.

Samarghandian S, Boskabady MH, Davoodi S (2010) Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line. Pharmacogn Mag 6(24):309–314PubMedCentralPubMedCrossRef

33.

Tarantillis PA, Morjani H, Polissiou M, Mafait M (1994) Inhibition of growth and induction of differentiation of HL-60 cells by carotenoids from Crocus sativus L. Anticancer Res 14:1913–1918

34.

Chryssanthi DG, Lamari FN, Iatrou G, Pylara A, Karamanos NK, Cordopatis P (2007) Inhibition of breast cancer cell proliferation by style constituents of different crocus species. Anticancer Res 27:357–362PubMed

35.

Nair SC, Panikkar B, Panikkar KR (1991) Antitumor activity of saffron. Cancer Lett 57:109–114PubMedCrossRef

36.

Aung HH, Wang CZ, Ni M, Fishbein A, Mehendale SR, Xie JT (2007) Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol 29(3):175–180PubMedCentralPubMed

37.

Bathaie SZ, Bolhassani A, Hoshyar R, Ranjbar B, Sabouni F, Moosavi-Movahedi AA (2007) Interaction of saffron carotenoids as anticancer compounds with ctDNA, Oligo (dG.dC)₁₅ and Oligo (dA.dT)₁₅. DNA Cell Biol 26(8):533–540PubMedCrossRef

38.

Salem ML (2005) Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol 5:1749–1770PubMedCrossRef

39.

Chew BP (1993) Role of carotenoids in the immune response. J Dairy Sci 76(9):2804–2811PubMedCrossRef

40.

Chew BP, Park JS (2004) Carotenoid action on the immune response. J Nutr 134(1):257S–261SPubMed

41.

Watzl B, Bub A, Brandstetter BR, Rechkemmer G (1999) Modulation of human T-lymphocyte functions by the consumption of carotenoid-rich vegetables. Br J Nutr 82:383–389PubMed

42.

Sepp T, Karu U, Sild E, Männiste M, Hõrak P (2011) Effects of carotenoids, immune activation and immune suppression on the intensity of chronic coccidiosis in greenfinches. Exp Parasitol 127(3):651–657PubMedCrossRef

43.

Perez-Rodriguez L, Mougeot F, Alonso-Alvarez C, Blas J, Viñuela J, Bortolotti GR (2008) Cell-mediated immune activation rapidly decreases plasma carotenoids but does not affect oxidative stress in red-legged partridges (Alectoris rufa). J Exp Biol 211:2155–2161PubMedCrossRef

44.

Bani S, Pandey A, Agnihotri VK, Pathania V, Singh B (2011) Selective Th2 up-regulation by crocus sativus: a neutraceutical spice. Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine, pp 1–9

Title: Chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96) DNA vaccine generates different anti-tumor effects against tumors expressing the E7 protein of human papillomavirus
Authors: Afshin Khavari
Azam Bolhassani
Fatemeh Alizadeh
S. Zahra Bathaie
Prabha Balaram
Elnaz Agi
Rouhollah Vahabpour
Publication date: 01-02-2015
Publisher: Springer Vienna
Published in: Archives of Virology / Issue 2/2015
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-014-2250-9

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