Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro

Objective. Perilla frutescens (L.) Brittis is a dietary herbal medicine and has anticancer effect. However, little is known about its anticancer peptides. This study is aimed at identifying cytotoxic oligopeptides which are loaded by a drug delivery system, to explore its anticancer application. Met...

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Main Authors: Dong-Liang He, Ri-Ya Jin, Hui-Zhen Li, Qing-Ye Liu, Zhi-Jun Zhang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:International Journal of Polymer Science
Online Access:http://dx.doi.org/10.1155/2018/1782734
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author Dong-Liang He
Ri-Ya Jin
Hui-Zhen Li
Qing-Ye Liu
Zhi-Jun Zhang
author_facet Dong-Liang He
Ri-Ya Jin
Hui-Zhen Li
Qing-Ye Liu
Zhi-Jun Zhang
author_sort Dong-Liang He
collection DOAJ
description Objective. Perilla frutescens (L.) Brittis is a dietary herbal medicine and has anticancer effect. However, little is known about its anticancer peptides. This study is aimed at identifying cytotoxic oligopeptides which are loaded by a drug delivery system, to explore its anticancer application. Methods. The oligopeptides were isolated from enzymatic hydrolysates of Perilla seed crude protein by using ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC). The structure of the oligopeptide was determined using a peptide sequencer, and its anticancer effect was examined by the MTT assay. PSO (Perilla seed oligopeptide), the most potent anticancer oligopeptide, was loaded by chitosan nanoparticles (NPs) modified by hyaluronic acid (HA). Then, the particle size, zeta potential, encapsulation efficiency (EE), drug loading efficiency (LE), the cumulative release rates of NPs, and its cytotoxic effect on cancer cells were investigated. Results. Three fractions were isolated by the chromatography assay. The third fraction has a broad-spectrum and the strongest anticancer effect. This fraction was further purified and identified as SGPVGLW with a molecular weight of 715 Da and named as PSO. Then, PSO was loaded by HA-conjugated chitosan to prepare HA/PSO/C NPs, which had a uniform size of 216.7 nm, a zeta potential of 35.4 mV, an EE of 38.7%, and an LE of 24.3%. HA/PSO/C NPs had a slow release rate in vitro, with cumulative release reaching to 81.1%. Compared with free PSO, HA/PSO/C NPs showed notably enhanced cytotoxicity and had the strongest potency to human glioma cell line U251. Conclusion. This study demonstrated that PSO, a novel oligopeptide from Perilla seeds, has a broad-spectrum anticancer effect and could be encapsulated by NPs, which enhanced tumor targeting cytotoxicity with obvious controlled release. Our study indicates that Perilla seeds are valuable for anticancer peptide development.
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spelling doaj-art-f873504f9a5846acb1f10c5a8cf045cd2025-02-03T05:48:23ZengWileyInternational Journal of Polymer Science1687-94221687-94302018-01-01201810.1155/2018/17827341782734Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In VitroDong-Liang He0Ri-Ya Jin1Hui-Zhen Li2Qing-Ye Liu3Zhi-Jun Zhang4School of Chemical Engineering and Technology, North University of China, Taiyuan, ChinaSchool of Chemical Engineering and Technology, North University of China, Taiyuan, ChinaSchool of Chemical Engineering and Technology, North University of China, Taiyuan, ChinaSchool of Chemical Engineering and Technology, North University of China, Taiyuan, ChinaSchool of Chemical Engineering and Technology, North University of China, Taiyuan, ChinaObjective. Perilla frutescens (L.) Brittis is a dietary herbal medicine and has anticancer effect. However, little is known about its anticancer peptides. This study is aimed at identifying cytotoxic oligopeptides which are loaded by a drug delivery system, to explore its anticancer application. Methods. The oligopeptides were isolated from enzymatic hydrolysates of Perilla seed crude protein by using ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC). The structure of the oligopeptide was determined using a peptide sequencer, and its anticancer effect was examined by the MTT assay. PSO (Perilla seed oligopeptide), the most potent anticancer oligopeptide, was loaded by chitosan nanoparticles (NPs) modified by hyaluronic acid (HA). Then, the particle size, zeta potential, encapsulation efficiency (EE), drug loading efficiency (LE), the cumulative release rates of NPs, and its cytotoxic effect on cancer cells were investigated. Results. Three fractions were isolated by the chromatography assay. The third fraction has a broad-spectrum and the strongest anticancer effect. This fraction was further purified and identified as SGPVGLW with a molecular weight of 715 Da and named as PSO. Then, PSO was loaded by HA-conjugated chitosan to prepare HA/PSO/C NPs, which had a uniform size of 216.7 nm, a zeta potential of 35.4 mV, an EE of 38.7%, and an LE of 24.3%. HA/PSO/C NPs had a slow release rate in vitro, with cumulative release reaching to 81.1%. Compared with free PSO, HA/PSO/C NPs showed notably enhanced cytotoxicity and had the strongest potency to human glioma cell line U251. Conclusion. This study demonstrated that PSO, a novel oligopeptide from Perilla seeds, has a broad-spectrum anticancer effect and could be encapsulated by NPs, which enhanced tumor targeting cytotoxicity with obvious controlled release. Our study indicates that Perilla seeds are valuable for anticancer peptide development.http://dx.doi.org/10.1155/2018/1782734
spellingShingle Dong-Liang He
Ri-Ya Jin
Hui-Zhen Li
Qing-Ye Liu
Zhi-Jun Zhang
Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro
International Journal of Polymer Science
title Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro
title_full Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro
title_fullStr Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro
title_full_unstemmed Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro
title_short Identification of a Novel Anticancer Oligopeptide from Perilla frutescens (L.) Britt. and Its Enhanced Anticancer Effect by Targeted Nanoparticles In Vitro
title_sort identification of a novel anticancer oligopeptide from perilla frutescens l britt and its enhanced anticancer effect by targeted nanoparticles in vitro
url http://dx.doi.org/10.1155/2018/1782734
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