Synergistic Antitumor Effect of Oligogalacturonides and Cisplatin on Human Lung Cancer A549 Cells.

Cian-Song Huang,Ping-Hsiu Huang,Diana Lo,Ming-Chang Wu,Yuh-Tai Wang,Ai-Chun Huang

doi:10.3390/ijms19061769

Abstract

Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of oligogalacturonides (OGA) and DDP on human lung cancer A549 cells. The combined use of OGA and DDP had a synergistic effect on the growth inhibition of A549 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + OGA 12 h. Western blot analyses showed that the combination treatment of OGA and DDP upregulated Bax, p53, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by OGA and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of OGA from natural sources and DDP could be an important new adjuvant therapy for lung cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.

Highlights

Lung cancer is one of the most common types of fatal malignancies worldwide and was estimated to be the leading cause of cancer deaths in 2016 in the United States [1,2]
The use of adjuvant therapies has not been optimized in lung cancer patients, it is expected to develop a broad availability of more targeted therapeutic treatment for lung cancer with limited damage to the immune system and natural barriers [3]
The cell proliferation of HEK293 and A549 cells was inhibited by 52.2% and 21.2%, respectively, at 8 μg/mL DDP, while 9.4% and 12.7% were inhibited, respectively, at 100 μg/mL OGA after 24 h of incubation

Summary

Introduction

Lung cancer is one of the most common types of fatal malignancies worldwide and was estimated to be the leading cause of cancer deaths in 2016 in the United States [1,2]. Chemotherapy is usually the main option for cancer patients with advanced stages of neoplasia; drug resistance and adverse side effects of chemotherapeutic agents influence the long-term outcomes of patients with advanced stage cancers [4]. Known as cisplatinum or cis-diamminedichloroplatinum (II), is one of the most effective chemotherapeutic drugs widely used for clinical cancer treatment including urinary bladder, head and neck, lung, ovarian, and testicular cancers. The common cisplatin concentration used for patients is 20–30 mg/m2, but in some cases that require a high dosage, the concentration can reach 80–120 mg/m2. The drug resistance and undesirable side effects retard the widespread utility of cisplatin (DDP), the combination of cisplatin with other chemical agents or compounds is used for many human cancers to overcome the drug resistance and considerable side effects [6,7]

Objectives

Results

Conclusion