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Article

Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines

by
Valentina Pagliara
1,†,
Rosarita Nasso
1,†,
Paola Di Donato
2,3,
Ilaria Finore
3,
Annarita Poli
3,
Mariorosario Masullo
1,4,* and
Rosaria Arcone
1,4,*
1
Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli “Parthenope”, Via Medina, 40, 80133 Napoli, Italy
2
Dipartimento di Scienze e Tecnologie, Università degli Studi di Napoli “Parthenope”, Centro Direzionale Isola C4, 80143 Napoli, Italy
3
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy
4
CEINGE, Biotecnologie Avanzate, S.C. a R.L., Via G., Salvatore, 486-80145 Napoli, Italy
*
Authors to whom correspondence should be addressed.
†
These authors equally contributed to this work.
Biomolecules 2019, 9(12), 833; https://doi.org/10.3390/biom9120833
Submission received: 4 November 2019 / Revised: 26 November 2019 / Accepted: 3 December 2019 / Published: 5 December 2019
(This article belongs to the Section Chemical Biology)
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Abstract

Among plant polyphenols, lemon peels extract (LPE) from the residues of the industrial processing of lemon (Citrus limon) shows anti-proliferative properties in cancer cells and anticholinesterase activity. In this study, we analyze the anti-cancer properties of LPE on migration and invasiveness in MKN-28 and AGS human gastric cancer cell lines either in the absence or presence of the pro-inflammatory cytokine IL-6. We find that the pretreatment with non-cytotoxic concentrations (0.5–1 μg/ml of gallic acid equivalent) of LPE inhibits interleukin-6 (IL-6)-induced cell migration and invasiveness in MKN-28 and AGS cells, as analyzed by wound and matrigel assays. Pretreatment with LPE is able to prevent either IL-6-induced matrix metalloproteinases (MMP)-9/2 activity, as assessed by gel zymography, or mRNA and protein MMP-9/2 expression, as evaluated by qPCR and Western blotting analysis, respectively. These LPE effects are associated with an IL-6-dependent STAT3 signaling pathway in MKN-28 and AGS cells. Furthermore, LPE shows acetylcholinesterase inhibitory activity when assayed by the Ellman method. In conclusion, our results demonstrate that LPE reduces the invasiveness of gastric MKN-28 and AGS cancer cells through the reduction of IL-6-induced MMP-9/2 up-regulation. Therefore, these data suggest that LPE exerts a protective role against the metastatic process in gastric cancer.
Keywords: lemon peel polyphenols; interleukin-6; matrix metalloproteinase-9; matrix metalloproteinase-2; gastric cancer cells; cell migration; cell invasiveness; acetylcholinesterase lemon peel polyphenols; interleukin-6; matrix metalloproteinase-9; matrix metalloproteinase-2; gastric cancer cells; cell migration; cell invasiveness; acetylcholinesterase
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MDPI and ACS Style

Pagliara, V.; Nasso, R.; Di Donato, P.; Finore, I.; Poli, A.; Masullo, M.; Arcone, R. Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines. Biomolecules 2019, 9, 833. https://doi.org/10.3390/biom9120833

AMA Style

Pagliara V, Nasso R, Di Donato P, Finore I, Poli A, Masullo M, Arcone R. Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines. Biomolecules. 2019; 9(12):833. https://doi.org/10.3390/biom9120833

Chicago/Turabian Style

Pagliara, Valentina, Rosarita Nasso, Paola Di Donato, Ilaria Finore, Annarita Poli, Mariorosario Masullo, and Rosaria Arcone. 2019. "Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines" Biomolecules 9, no. 12: 833. https://doi.org/10.3390/biom9120833

APA Style

Pagliara, V., Nasso, R., Di Donato, P., Finore, I., Poli, A., Masullo, M., & Arcone, R. (2019). Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines. Biomolecules, 9(12), 833. https://doi.org/10.3390/biom9120833

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