Biochemical and Biophysical Research Communications
Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo
Introduction
Lung squamous cell carcinoma (SCC) is a common type of non-small-cell lung cancer (NSCLC) and the second leading cause of death associated with lung cancer [1], [2]. There are not yet any approved targeted therapies for SCC and few advances have resulted in better therapeutic options for SCC [3]. Thus, finding effective therapeutic strategy is urgently necessary for preventing SCC.
Aloe-emodin (AE, 1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is a bioactive anthraquinone, derived from both Aloe vera and Rheum officinale, and recently has been suggested to have various pharmacological activities [4]. AE has attracted much attention for its remarkable antineoplastic activity on different tumor cells, including lung, hepatic and colon cancers, through multi-channel molecular mechanisms, such as the induction of apoptosis, disruption of cell cycle, anti-metastasis, and enhancement of immune function [5], [6]. However, the toxicity, pharmacokinetic behavior, and molecular mechanisms of this drug have not been fully understood so far. Additionally, AE plays as a sensitizer for chemotherapy and radiation in cancer therapy [7]. Unfortunately, due to its hydrophobic property, it is not convenient to carry out intravascular administration of AE, exhibiting poor pharmacokinetics, low bioavailability and bad absorption [8]. Hence, looking for effective methods to attenuate these limitations is required for obtaining better efficacy of AE for cancer treatment.
Recently, novel drug delivery systems have shown superior advances in improving drugs' efficacy as well as patients' compliance [9]. Nanoparticle technology supplies an effective method to deliver anti-cancer drugs into tumors [10]. To circumvent AE's inherent issues, AE nanoparticles formulation (NanoAE) were prepared according to poly (lactic-co-glycolic acid) (PLGA). The formulation has been suggested to be effective for improving therapeutic effects in cancer cells [11]. Here, we attempted to implement nanoAE formulation to obtain improved anti-cancerous effects on SCC. We found that nanoAE effectively suppressed the growth of SCC cells, arrested cell cycle in the G1/S and G2/M transition phase, triggered apoptosis, associated with elevated ROS generation. NanoAE might be a beneficial treatment for the overall management of SCC.
Section snippets
Cells culture
Human SCC cell lines of H520, H226, SK-MES-1 and H1299, as well as human bronchial epithelial cell of BEAS-2B were all obtained from American Type Culture Collection (ATCC, USA) and maintained in RPMI-1640 or DMEM medium (Gibco, USA) with 10% fetal bovine serum in a humidified CO2 incubator under 5% CO2 for further study.
Cell viability analysis
2 × 104 cells/well were seeded on plates and incubated at 37 °C overnight under an atmosphere of 95% air and 5% CO2, and treated with various concentration of nanoAE for 24 h.
The preparation of aloe-emodin nanoparticles (NanoAE) and its effects on the cell proliferation of human lung squamous carcinoma
In order to calculate the AE's role in preventing human lung squamous carcinoma, the AE nanoparticles were formulated (NanoAE), which was based on PLGA (Fig. 1A). The transmission electron microscopy (TEM) was used to observe the morphology of AE nanoparticles (Fig. 1B). The particle size distribution of freshly-prepared nanoAE was 42 nm, which revealed the narrow particle size distribution of nanoAE (Fig. 1C). As shown in Fig. 1D, the zeta potential of nanoparticles was −21.2 mv. Fluorescent
Discussion
Conventional cytotoxic chemotherapy and radiation therapy to patients with squamous non-small-cell lung cancer are limited due to eventual development of systemic toxicity and drug resistance [5]. Thus, it is required to implement biologically safe and effective natural components as anti-tumor and chemo-preventive drugs, widely applied in human. Aloe-emodin (AE) is a novel anthraquinone compound, derived from traditional Chinese medicine plants, and has been suggested to have anticancer
References (26)
- et al.
Acitretin and aloe-emodin loaded chitin nanogel for the treatment of psoriasis
Eur. J. Pharm. Biophar
(2016) - et al.
An overview of clinical and commercial impact of drug delivery systems
J. Control. Release
(2014) - et al.
Hybrid poly (lactic-co-glycolic acid) nanoparticles: design and delivery prospectives
Drug Discov. Today
(2015) - et al.
HOXB13 contributes to G1/S and G2/M checkpoint controls in prostate
Mol. Cell. Endocrinol.
(2014) - et al.
Acetylation of p53 protein at lysine 120 up-regulates Apaf-1 protein and sensitizes the mitochondrial apoptotic pathway
J. Biol. Chem.
(2016) - et al.
Cryptotanshinone induces melanoma cancer cells apoptosis via ROS-mitochondrial apoptotic pathway and impairs cell migration and invasion
Biomed. Pharm.
(2016) - et al.
Palmitate promotes autophagy and apoptosis through ROS-dependent JNK and p38 MAPK
Biochem. Bioph. Res. Co.
(2015) - et al.
Zinc oxide nanoparticles induce apoptosis by enhancement of autophagy via PI3K/Akt/mTOR inhibition
Toxicol. Lett.
(2014) - et al.
Herbacetin induces apoptosis in HepG2 cells: involvements of ROS and PI3K/Akt pathway
Food Chem. Toxicol.
(2013) - et al.
Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence
Trends Biochem. Sci.
(2014)