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Plant Foods for Human Nutrition

, Volume 74, Issue 2, pp 164–170 | Cite as

Capsaicin in Hot Chili Peppers: In Vitro Evaluation of Its Antiradical, Antiproliferative and Apoptotic Activities

  • Margherita Lavorgna
  • Elena Orlo
  • Roberta Nugnes
  • Concetta Piscitelli
  • Chiara Russo
  • Marina IsidoriEmail author
Original Paper

Abstract

Capsaicin is a spicy capsaicinoid, produced as secondary metabolite by Capsicum fruits. This alkaloid has been used for years in folk medicine for its analgesic and antinflammatory properties although most data is referred to the raw fruit. In this study, the antiradical activity of the pure capsaicin has been studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays as well as its antiproliferative activity, using MTT assay, against two human tumour cell lines, the colorectal Caco-2 and the oesophageal OE19 cells. Furthermore, the antiproliferative activity observed on tumoral cells was compared with that of the human normal-like fibroblast cell line TelCOFS02MA. In addition, the apoptotic activity was evaluated using TUNEL assay. A higher radical scavenging activity was observed against ABTS radical cation than DPPH. Capsaicin showed also a higher cytotoxicity against cancer cells than normal-like cells with Selectivity index values greater than 2 at 72 h. Capsaicin induced apoptosis especially in OE19 cell line.

Keywords

Capsicum annuum Antiradical activity Cytotoxicity Selectivity index Tumor cells Normal-like cells 

Abbreviations

ABTS

2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)

ATCC

American type culture collection

DFI

DNA Fragmentation index

DMEM

Dulbecco’s modified eagle medium

DPPH

2,2-diphenyl-1-picrylhydrazyl

EC50

Median effective concentration

FBS

Fetal bovine serum

HEPES

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

IC50

Median inhibition concentration

MEM

Minimum essential medium amino acids solution

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NC

Negative control

NF-kB

Nuclear factor kappa B

RPMI

Roswell park memorial institute 1640 medium

SI

Selectivity index

TEAC

Trolox equivalent antioxidant capacity

TROLOX

6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

TUNEL

Terminal deoxynucleotidyl transferase dUTP nick end labeling

Notes

Acknowledgments

This work has been supported by the University of Campania ‘Luigi Vanvitelli’.

Compliance with Ethical Standards

Conflict of Interest

The authors Margherita Lavorgna, Elena Orlo, Roberta Nugnes, Concetta Piscitelli, Chiara Russo, Marina Isidori declare that they have no conflict of interest.

Supplementary material

11130_2019_722_MOESM1_ESM.docx (116 kb)
ESM 1 (DOCX 115 kb)

References

  1. 1.
    Popelka P, Jevinová P, Šmejkal K, Roba P (2017) Determination of capsaicin content and pungency level of different fresh and dried chilli peppers. Folia Vet 61(2):11–16.  https://doi.org/10.1515/fv-2017-0012
  2. 2.
    Brederson JD, Kym PR, Szallasi A (2013) Targeting TRP channels for pain relief. Eur J Pharmacol 716(1–3):61–76.  https://doi.org/10.1016/j.ejphar.2013.03.003 CrossRefGoogle Scholar
  3. 3.
    Galano A, Martinez A (2012) Capsaicin, a tasty free radical scavenger: mechanism of action and kinetics. J Phys Chem B 116(3):1200–1208.  https://doi.org/10.1021/jp211172f CrossRefGoogle Scholar
  4. 4.
    Kang JH, Kim CS, Han IS, Kawada T, Yu R (2007) Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett 581(23):4389–4396.  https://doi.org/10.1016/j.febslet.2007.07.082 CrossRefGoogle Scholar
  5. 5.
    Surh YJ (2002) Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol 40(8):1091–1097.  https://doi.org/10.1016/S0278-6915(02)00037-6 CrossRefGoogle Scholar
  6. 6.
    Sancho R, Lucena C, Macho A, Calzado MA, Blanco-Molina M, Minassi A, Appendino G, Munoz E (2002) Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent antiinflammatory compound in vivo. Eur J Immunol 32(6):1753–1763.  https://doi.org/10.1002/1521-4141(200206)32:6<1753::AID-IMMU1753>3.0.CO;2-2 CrossRefGoogle Scholar
  7. 7.
    Rosa A, Deiana M, Casu V, Paccagnini S, Appendino G, Ballero M, Dessi MA (2002) Antioxidant activity of capsinoids. J Agric Food Chem 50(25):7396–7401 http://pubs.acs.org/doi/abs/10.1021/jf020431w CrossRefGoogle Scholar
  8. 8.
    Abadio Finco FD, Kammerer DR, Carle R, Tseng WH, Boser S, Graeve L (2012) Antioxidant activity and characterization of phenolic compounds from bacaba (Oenocarpus bacaba Mart.) fruit by HPLC-DAD-MS(n). J Agric Food Chem 60(31):7665–7673.  https://doi.org/10.1021/jf3007689
  9. 9.
    Murakami K, Ito M, Htay HH, Tsubouchi R, Yoshino M (2001) Antioxidant effect of capsaicinoids on the metal-catalyzed lipid peroxidation. Biomed Res 22(1):15–17.  https://doi.org/10.2220/biomedres.22.15
  10. 10.
    Kempaiah RK, Manjunatha H, Srinivasan K (2005) Protective effect of dietary capsaicin on induced oxidation of low-density lipoprotein in rats. Mol Cell Biochem 275(1–2):7–13.  https://doi.org/10.1007/s11010-005-7643-3 CrossRefGoogle Scholar
  11. 11.
    Jung MY, Kang HJ, Moon A (2001) Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett 165(2):139–145.  https://doi.org/10.1016/S0304-3835(01)00426-8 CrossRefGoogle Scholar
  12. 12.
    Lo YC, Yang YC, Wu IC, Kuo FC, Liu CM, Wang HW, Kuo CH, Wu JY, Wu DC (2005) Capsaicin-induced cell death in a human gastric adenocarcinoma cell line. World J Gastroenterol 11(40):6254–6257.  https://doi.org/10.3748/wjg.v11.i40.6254 CrossRefGoogle Scholar
  13. 13.
    Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa K, Sakurada K, Nakagata N, Ikeda Y, Mak TW, Suda T (2004) Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431(7011):997–1002.  https://doi.org/10.1038/nature02989 CrossRefGoogle Scholar
  14. 14.
    Amantini C, Ballarini P, Caprodossi S, Nabissi M, Morelli MB, Lucciarini R, Cardarelli MA, Mammana G, Santoni G (2009) Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis 30(8):1320–1329.  https://doi.org/10.1093/carcin/bgp138 CrossRefGoogle Scholar
  15. 15.
    Yang KM, Pyo JO, Kim GY, Yu R, Han IS, Ju SA, Kim WH, Kim BS (2009) Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines. Cell Mol Biol Lett 14(3):497–510.  https://doi.org/10.2478/s11658-009-0016-2 CrossRefGoogle Scholar
  16. 16.
    Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK (2008) In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13(12):1465–1478.  https://doi.org/10.1007/s10495-008-0278-6 CrossRefGoogle Scholar
  17. 17.
    Pramanik KC, Boreddy SR, Srivastava SK (2011) Role of mitochondrial electron transport chain complexes in capsaicin mediated oxidative stress leading to apoptosis in pancreatic cancer cells. PLoS One 6(5):e20151.  https://doi.org/10.1371/journal.pone.0020151 CrossRefGoogle Scholar
  18. 18.
    Chen D, Yang Z, Wang Y, Zhu G, Wang X (2012) Capsaicin induces cycle arrest by inhibiting cyclin-dependent-kinase in bladder carcinoma cells. Int J Urol 19(7):662–668.  https://doi.org/10.1111/j.1442-2042.2012.02981.x CrossRefGoogle Scholar
  19. 19.
    Sanchez AM, Malagarie-Cazenave S, Olea N, Vara D, Chiloeches A, Diaz-Laviada I (2007) Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation. Apoptosis 12(11):2013–2024.  https://doi.org/10.1007/s10495-007-0119-z CrossRefGoogle Scholar
  20. 20.
    Wu CC, Lin JP, Yang JS, Chou ST, Chen SC, Lin YT, Lin HL, Chung JG (2006) Capsaicin induced cell cycle arrest and apoptosis in human esophagus epidermoid carcinoma CE 81T/VGH cells through the elevation of intracellular reactive oxygen species and Ca2+ productions and caspase-3 activation. Mutat Res 601(1–2):71–82.  https://doi.org/10.1016/j.mrfmmm.2006.06.015 CrossRefGoogle Scholar
  21. 21.
    Tsou MF, Lu HF, Chen SC, Wu LT, Chen YS, Kuo HM, Lin SS, Chung JG (2006) Involvement of Bax, Bcl-2, Ca2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells. Anticancer Res 26(3A):1965–1971Google Scholar
  22. 22.
    Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 28(1):25–30.  https://doi.org/10.1016/S0023-6438(95)80008-5
  23. 23.
    Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26(9–10):1231–1237.  https://doi.org/10.1016/S0891-5849(98)00315-3 CrossRefGoogle Scholar
  24. 24.
    Baharum Z, Akim AM, Taufiq-Yap YH, Hamid RA, Kasran R (2014) In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao. Molecules 19(11):18317–18331.  https://doi.org/10.3390/molecules191118317
  25. 25.
    Demirgan R, Karagöz A, Pekmez M, Önay-Uçar E, Artun FT, Gürer Ç, Mat A (2016) In vitro anticancer activity and cytotoxicity of some papaver alkaloids on cancer and normal cell lines. Afr J Tradit Complement Altern Med 13(3):22–26.  https://doi.org/10.4314/ajtcam.v13i3.3 CrossRefGoogle Scholar
  26. 26.
    Rocco L, Peluso C, Cesaroni F, Morra N (2012) Genomic damage in human sperm cells exposed in vitro to environmental pollutants. J Environ Anal Toxicol 2(1):117.  https://doi.org/10.4172/2161-0525.1000117 CrossRefGoogle Scholar
  27. 27.
    Zimmer AR, Leonardi B, Miron D, Schapoval E, Oliveira JR, Gosmann G (2012) Antioxidant and anti-inflammatory properties of Capsicum baccatum: from traditional use to scientific approach. J Ethnopharmacol 139(1):228–233.  https://doi.org/10.1016/j.jep.2011.11.005
  28. 28.
    Perucka I, Materska M (2003) Antioxidant activity and content of capsaicinoids isolated from paprika fruits. Pol J Food Nutr Sci 12(53):15–18.  https://doi.org/10.1021/jf035331k
  29. 29.
    Bley K, Boorman G, Mohammad B, McKenzie D, Babbar S (2012) A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol 40(6):847–873.  https://doi.org/10.1177/0192623312444471 CrossRefGoogle Scholar
  30. 30.
    Clark R, Lee SH (2016) Anticancer properties of capsaicin against human cancer. Anticancer Res 36(3):837–843.  https://doi.org/10.1124/jpet.117.243691
  31. 31.
    Ahmed SS, Faten ZM, Al-shimaa MA (2017) In vitro studies on anticancer activity of capsaicin a component of hot chili pepper against human hepatocellular carcinoma cells. Int J Cell Sci & Mol Biol 2(4):555591.  https://doi.org/10.19080/IJCSMB.2017.02.555591
  32. 32.
     Al-Suhaibani ES, El-Morshedi NA (2015) Apoptotic effect of capsaicin on colon cancer (Caco-2) cells via Bcl-2, P53 and caspase-3 pathways. Int J Sci Res 4(4):2283–2287Google Scholar
  33. 33.
    Marques CMG, Dibden C, Danson S, Haycock JW, MacNeil S (2013) Combined effects of capsaicin and HA14-1 in inducing apoptosis in melanoma cells. JCDSA 3(3):175–189.  https://doi.org/10.4236/jcdsa.2013.33028
  34. 34.
    Jin J, Lin G, Huang H, Xu D, Yu H, Ma X, Zhu L, Ma D, Jiang H (2014) Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53. Int J Biol Sci 10(3):285–295.  https://doi.org/10.7150/ijbs.7730 CrossRefGoogle Scholar
  35. 35.
    Kim MY, Trudel LJ, Wogan GN (2009) Apoptosis induced by capsaicin and resveratrol in colon carcinoma cells requires nitric oxide production and caspase activation. Anticancer Res 29(10):3733–3740Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Margherita Lavorgna
    • 1
  • Elena Orlo
    • 1
  • Roberta Nugnes
    • 1
  • Concetta Piscitelli
    • 1
  • Chiara Russo
    • 1
  • Marina Isidori
    • 1
    Email author
  1. 1.Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e FarmaceuticheUniversità della Campania “L. Vanvitelli”CasertaItaly

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