Oral Administration of Fermented Papaya (FPP) Controls the Growth of a Murine Melanoma Through the In Vivo Induction of a Natural Antioxidant Response

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Jan 24

PMID 30669508

Citations 8

Authors

Mariantonia Logozzi

Davide Mizzoni

Rossella Di Raimo

Daniele Macchia

Massimo Spada

Stefano Fais

Affiliations

Soon will be listed here.

Abstract

Prolonged oxidative stress may play a key role in tumor development. Antioxidant molecules are contained in many foods and seem to have a potential role in future anti-tumor strategies. Among the natural antioxidants the beneficial effect of Fermented Papaya (FPP) is well known. The aim of this study was to investigate the effects of orally administered FPP in either the prevention or treatment of a murine model of melanoma. The tumor growth was analyzed together with the blood levels of both oxidants (ROS) and anti-oxidants (SOD-1 and GSH). The results showed that FPP controlled tumor growth, reducing the tumor mass of about three to seven times vs. untreated mice. The most significant effect was obtained with sublingual administration of FPP close to the inoculation of melanoma. At the time of the sacrifice none of mice treated with FPP had metastases and the subcutaneous tumors were significantly smaller and amelanotic, compared to untreated mice. Moreover, the FPP anti-tumor effect was consistent with the decrease of total ROS levels and the increase in the blood levels of GSH and SOD-1. This study shows that a potent anti-oxidant treatment through FPP may contribute to both preventing and inhibiting tumors growth.

Citing Articles

Antioxidant Effect of a Plant-Derived Extracellular Vesicles' Mix on Human Skin Fibroblasts: Induction of a Reparative Process.

Di Raimo R, Mizzoni D, Aloi A, Pietrangelo G, Dolo V, Poppa G Antioxidants (Basel). 2024; 13(11).

PMID: 39594515 PMC: 11590891. DOI: 10.3390/antiox13111373.

The Leucocyte Telomere Length, and Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease.

Tacheva T, Zienolddiny-Narui S, Dimov D, Vlaykova D, Miteva I, Vlaykova T Curr Issues Mol Biol. 2022; 44(8):3757-3769.

PMID: 36005153 PMC: 9406937. DOI: 10.3390/cimb44080257.

Benefits of Fermented Papaya in Human Health.

Leitao M, Ribeiro T, Garcia P, Barreiros L, Correia P Foods. 2022; 11(4).

PMID: 35206040 PMC: 8870802. DOI: 10.3390/foods11040563.

Thirty years of translational research in Mobility Medicine: Collection of abstracts of the 2020 Padua Muscle Days.

Carraro U Eur J Transl Myol. 2020; 30(1):8826.

PMID: 32499887 PMC: 7254447. DOI: 10.4081/ejtm.2019.8826.

antiaging effects of alkaline water supplementation.

Logozzi M, Mizzoni D, Di Raimo R, Andreotti M, Macchia D, Spada M J Enzyme Inhib Med Chem. 2020; 35(1):657-664.

PMID: 32106720 PMC: 7054916. DOI: 10.1080/14756366.2020.1733547.

References

Rimbach G, Guo Q, Akiyama T, Matsugo S, Moini H, Virgili F . Ferric nitrilotriacetate induced DNA and protein damage: inhibitory effect of a fermented papaya preparation. Anticancer Res. 2000; 20(5A):2907-14. View

Brown A, Dinger N, Levine B . Stress produced by gavage administration in the rat. Contemp Top Lab Anim Sci. 2001; 39(1):17-21. View

Murphy S, Smith P, Shaivitz A, Rossberg M, Hurn P . The effect of brief halothane anesthesia during daily gavage on complications and body weight in rats. Contemp Top Lab Anim Sci. 2001; 40(2):9-12. View

Ching L, Mohamed S . Alpha-tocopherol content in 62 edible tropical plants. J Agric Food Chem. 2001; 49(6):3101-5. DOI: 10.1021/jf000891u. View

Miean K, Mohamed S . Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem. 2001; 49(6):3106-12. DOI: 10.1021/jf000892m. View

La Vecchia C, Altieri A, Tavani A . Vegetables, fruit, antioxidants and cancer: a review of Italian studies. Eur J Nutr. 2002; 40(6):261-7. DOI: 10.1007/s394-001-8354-9. View

Coussens L, Werb Z . Inflammation and cancer. Nature. 2002; 420(6917):860-7. PMC: 2803035. DOI: 10.1038/nature01322. View

Rimbach G, Park Y, Guo Q, Moini H, Qureshi N, Saliou C . Nitric oxide synthesis and TNF-alpha secretion in RAW 264.7 macrophages: mode of action of a fermented papaya preparation. Life Sci. 2003; 67(6):679-94. DOI: 10.1016/s0024-3205(00)00664-0. View

Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A . Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004; 96(22):1702-13. DOI: 10.1093/jnci/djh305. View

10.

Gillies R, Raghunand N, Garcia-Martin M, Gatenby R . pH imaging. A review of pH measurement methods and applications in cancers. IEEE Eng Med Biol Mag. 2004; 23(5):57-64. DOI: 10.1109/memb.2004.1360409. View

11.

Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M . Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006; 160(1):1-40. DOI: 10.1016/j.cbi.2005.12.009. View

12.

Kawanishi S, Hiraku Y . Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation. Antioxid Redox Signal. 2006; 8(5-6):1047-58. DOI: 10.1089/ars.2006.8.1047. View

13.

Aruoma O, Colognato R, Fontana I, Gartlon J, Migliore L, Koike K . Molecular effects of fermented papaya preparation on oxidative damage, MAP Kinase activation and modulation of the benzo[a]pyrene mediated genotoxicity. Biofactors. 2006; 26(2):147-59. DOI: 10.1002/biof.5520260205. View

14.

Nunomura A, Castellani R, Zhu X, Moreira P, Perry G, Smith M . Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol. 2006; 65(7):631-41. DOI: 10.1097/01.jnen.0000228136.58062.bf. View

15.

Basu A, Imrhan V . Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials. Eur J Clin Nutr. 2006; 61(3):295-303. DOI: 10.1038/sj.ejcn.1602510. View

16.

Schumacker P . Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell. 2006; 10(3):175-6. DOI: 10.1016/j.ccr.2006.08.015. View

17.

Halliwell B . Oxidative stress and cancer: have we moved forward?. Biochem J. 2006; 401(1):1-11. DOI: 10.1042/BJ20061131. View

18.

Marotta F, Yoshida C, Barreto R, Naito Y, Packer L . Oxidative-inflammatory damage in cirrhosis: effect of vitamin E and a fermented papaya preparation. J Gastroenterol Hepatol. 2007; 22(5):697-703. DOI: 10.1111/j.1440-1746.2007.04937.x. View

19.

Nakamura Y, Yoshimoto M, Murata Y, Shimoishi Y, Asai Y, Park E . Papaya seed represents a rich source of biologically active isothiocyanate. J Agric Food Chem. 2007; 55(11):4407-13. DOI: 10.1021/jf070159w. View

20.

De Milito A, Iessi E, Logozzi M, Lozupone F, Spada M, Marino M . Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. Cancer Res. 2007; 67(11):5408-17. DOI: 10.1158/0008-5472.CAN-06-4095. View