Lobaplatin induces BGC-823 human gastric carcinoma cell apoptosis via ROS- mitochondrial apoptotic pathway and impairs cell migration and invasion
Introduction
Human gastric carcinoma, or stomach carcinoma, is the fifth most common type of cancer overall, with an estimated 952,000 new cases worldwide in 2012. There were estimated 723,000 deaths from gastric carcinoma in 2012, accounting for 8.8% of all sexes cancer deaths and ranking third [1]. It is estimated that 420,489 men and women were diagnosed with gastric cancer in China in 2011, accounting for 12.47% of all new cancer cases [2]. High-incidence areas include East Asia, Eastern Europe, Central and South America, Japan and Korea, which is considered to mostly be associated with variations in diet [3], [4]. In spite of the declined worldwide mortality rates of gastric carcinoma in the last decade, the survival rate remains low [5].
Among other third-generation platinum antineoplastic agents, lobaplation received only regional approval. Lobaplatin was approved in China for the therapy of metastatic breast cancer, chronic myelogenous leukemia and small cell lung cancer. Its dose-limited toxicity is thrombocytopenia [6], [7]. Except these diseases, some clinical trials and published researches exhibited that lobaplation also had antitumor activities in many other tumor types, such as human esophageal cancer, ovarian cancer, colorectal carcinoma, hepatocellular carcinoma, cholangio carcinoma, and cervical cancer, melanoma, etc [8], [9], [10], [11], [12], [13].
However, there is limited evidence for the effects of lobaplation on the underlying mechanisms in human gastric cancer [14]. The aim of present study was to clarify the mode of action of lobaplation in the context of its anti-tumor activity, which could provide more evidences for the clinical application of lobaplatin in human gastric cancer treatment.
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Reagents and chemicals
Lobaplatin was purchased from Hainan Chang’an International Pharmaceutical Co., Ltd. (China). 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT), dimethyl sulfoxide (DMSO), propidium iodide (PI), Rhodamine-123 (Rh123) and 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) were purchased from Sigma (St Louis, MO). The following primary antibodies were used in this research: Bcl-2, Bax, Cleaved caspase-3, MMP9 and MMP2 were purchased from Cell Signaling Technology Company
Lobaplatin inhibited BGC-823 cells proliferation and influenced the cell morphology
The chemical structure of lobaplatin was shown in Fig. 1. Prior to investigating the pharmacological potential of lobaplatin for affecting human gastric cancer cell viability, we first assayed the cytotoxicity of lobaplatin by treating BGC-823 cells with different concentrations (0, 1, 2, 4, 8, 16 and 32 μg/mL) for 24, 48 and 72 h using an MTT assay. As shown in Fig. 2A, lobaplatin inhibited the growth of BGC-823 cells in concentration- and time-dependent manner. What’s more, decreased
Discussion and conclusion
It had been well known that gastric cancer leaded the fifth-most cancer. Its incidence rate in Asia is higher than North America, whereas mortality rate are consistently high in all parts of the world [28]. Risk factors for stomach cancers include H. pylori and Epstein-Barr virus infection, low socioeconomic status, smoking, intake of salty and smoked food, low consumption of fruits and vegetables, et al. [29], [30], [31], [32], [33], [34]. Effective prevention strategies have been implemented,
Disclosure of interest
The authors declare no competing interests.
Acknowledgements
We gratefully acknowledge Boguang Sun for helping in cell culturing. This study was funded by the grants from the National Natural Science Foundation of China (81500054), China Postdoctoral Science Foundation (2015M570788, 2016T90859) and Undergraduate Innovation Project of Sichuan University (201510610647).
References (48)
- et al.
Lobaplatin suppresses proliferation and induces apoptosis in the human colorectal carcinoma cell Line LOVO in vitro
Biomed. Pharmacother.
(2011) - et al.
Lobaplatin arrests cell cycle progression, induces apoptosis and alters the proteome in human cervical cancer cell Line CaSki
Biomed. Pharmacother.
(2014) - et al.
Lobaplatin induces apoptosis and arrests cell cycle progression in human cholangiocarcinoma cell line RBE
Biomed. Pharmacother.
(2012) - et al.
Lobaplatin arrests cell cycle progression, induces apoptosis and impairs migration and invasion in B16-F10 melanoma cell line in vitro
Biomed. Pharmacother.
(2015) - et al.
Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro
Biomed. Pharmacother.
(2016) - et al.
Death without caspases, caspases without death
Trends Cell Biol.
(2004) - et al.
Free radicals, metals and antioxidants in oxidative stress-induced cancer
Chem. Biol. Interact.
(2006) - et al.
World Cancer Report 2014
(2014) - et al.
Annual report on status of cancer in China, 2011
Chin. J. Cancer Res.
(2015) - et al.
Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention
Cancer Epidemiol. Biomarkers Prev.
(2014)
Epidemiology of gastric cancer
World J. Gastroenterol.
Current issues in gastric cancer epidemiology
Rev. Med. Chir. Soc. Med. Nat. Iasi.
Platinum-based drugs: past, present and future
Cancer Chemother. Pharmacol.
The status of platinum anticancer drugs in the clinic and in clinical trials
Dalton Trans.
Lobaplatin: a new antitumour platinum drug
Expert. Opin. Invest. Drugs
Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells
J. Hematol. Oncol.
Lobaplatin inhibits growth of gastric cancer cells by inducing apoptosis
World J. Gastroenterol.
The Anthelmintic drug niclosamide induces apoptosis, impairs metastasis and reduces immunosuppressive cells in breast cancer model
PLoS One
The migrastatin family: discovery of potent cell migration inhibitors by chemical synthesis
J. Am. Chem. Soc.
Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
Oncotarget
SKLB-163, a new benzothiazole-2-thiol derivative, exhibits potent anticancer activity by affecting RhoGDI/JNK-1 signaling pathway
Cell Death Dis.
Nifuroxazide induces apoptosis and impairs pulmonary metastasis in breast cancer model
Cell Death Dis.
A novel small-molecule YLT205 induces apoptosis in human colorectal cells via mitochondrial apoptosis pathway in vitro and inhibits tumor growth in vivo
Cell. Physiol. Biochem.
The novel protective role of P27 in MLN4924-treated gastric cancer cells
Cell Death Dis.
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These authors contributed equally to this study.