Gefitinib and curcumin-loaded nanoparticles enhance cell apoptosis in human oral cancer SAS cells in vitro and inhibit SAS cell xenografted tumor in vivo

Kuang-Chi Lai; Fu-Shin Chueh; Yung-Ting Hsiao; Zheng-Yu Cheng; Jin-Cherng Lien; Kuo-Ching Liu; Shu-Fen Peng; Jing-Gung Chung

doi:10.1016/j.taap.2019.114734

Gefitinib and curcumin-loaded nanoparticles enhance cell apoptosis in human oral cancer SAS cells in vitro and inhibit SAS cell xenografted tumor in vivo

Toxicol Appl Pharmacol. 2019 Nov 1:382:114734. doi: 10.1016/j.taap.2019.114734. Epub 2019 Aug 27.

Authors

Kuang-Chi Lai¹, Fu-Shin Chueh², Yung-Ting Hsiao³, Zheng-Yu Cheng³, Jin-Cherng Lien⁴, Kuo-Ching Liu⁵, Shu-Fen Peng⁶, Jing-Gung Chung⁷

Affiliations

¹ Department of Medical Laboratory Science and Biotechnology, College of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan; Department of Surgery, China Medical University Beigang Hospital, Beigang, Yunlin, Taiwan.
² Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan.
³ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
⁴ Department of School of Pharmacy, China Medical University, Taichung, Taiwan.
⁵ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
⁶ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: t20811@mail.cmuh.org.tw.
⁷ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: jgchung@mail.cmu.edu.tw.

PMID: 31470033
DOI: 10.1016/j.taap.2019.114734

Abstract

Curcumin (Cur), a natural product, has been shown to have anti-tumor activities in many human cancer cells. Gefitinib (Gef) is a clinical drug for cancer patients. However, there is no available information to show whether Gef/Cur nanoparticles (NPs) increased cell apoptosis and anti-tumor effects on xenograft mice model in vivo. In this study, γ-polyglutamic acid-coated nanoparticles loaded with Gef and Cur (γ-PGA-Gef/Cur NPs) were developed and its physicochemical properties and antitumor effects were investigated in vitro and in vivo. The γ-PGA-Gef/Cur NPs showed 548.5 ± 93.7 nm in diameter and -40.3 ± 3.87 mV on surface charge. The loading efficiencies of Gef and Cur were 89.5 and 100%, respectively. γ-PGA-Gef/Cur NPs could be internalized into SAS cells and significantly decreased total cell viability of SAS cells. Western blotting results indicated that both free Gef/Cur and γ-PGA-Gef/Cur NPs induced apoptotic cell death via caspase- and mitochondria-dependent pathways. In vivo studies indicated that treatments of PLGA NPs, free Gef/Cur, and γ-PGA-Gef/Cur NPs did not significantly affect appearances and bodyweights of mice. But the γ-PGA-Gef/Cur NPs significantly suppressed tumor size when comparing to free Gef/Cur-treated group. The nanoparticles developed in this study may be used as a potential therapy for oral cancer.

Keywords: Apoptosis; Curcumin; Gefitinib; SAS human oral cancer cells; γ-PGA-Cur/Gef nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Antineoplastic Agents / administration & dosage
Apoptosis / drug effects*
Apoptosis / physiology
Curcumin / administration & dosage*
Gefitinib / administration & dosage*
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms / drug therapy*
Mouth Neoplasms / pathology
Nanoparticles / administration & dosage*
Protein Kinase Inhibitors / administration & dosage
Xenograft Model Antitumor Assays / methods*

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Protein Kinase Inhibitors
Curcumin
Gefitinib