The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer.

Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.

Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer.

Gastric cancer (GC) is a malignant cancer of the digestive tract and is a life-threatening disease worldwide. Ferroptosis is a newly discovered form of regulated cell death, which involves the accumulation of iron-dependent lipid peroxides. It has been found that ferroptosis plays an important regulatory role in the occurrence, development, drug resistance, and prognosis of GC. Non-coding RNAs (ncRNAs) play a critical role in the occurrence and progression of a variety of diseases including GC. In recent years, the role of ferroptosis and ferroptosis-related ncRNAs (miRNA, lncRNA, and circRNA) in the occurrence, development, drug resistance, and prognosis of GC has attracted more and more attention. Herein, we briefly summarize the roles and functions of ferroptosis and ferroptosis-related ncRNAs in GC tumorigenesis, development, and prognosis. We also prospected the future research direction and challenges of ferroptosis and ferroptosis-related ncRNAs in GC.

Exosomes and Exosomal circRNAs: The Rising Stars in the Progression, Diagnosis and Prognosis of Gastric Cancer.

Gastric cancer (GC) is a common malignant tumor affecting human health, with occult onset and poor prognosis. Exosomes are extracellular vesicles secreted by almost all cells, which can reflect the state of source cells or tissues. It is reported that exosomes are involved in almost all processes of GC. Exosomes provided a window to understand changes in cell or tissue states by carrying active components such as circular RNAs (circRNAs). CircRNAs are a naturally occurring class of endogenous noncoding RNAs and abnormal expression during the occurrence and development of GC. Exosomal circRNAs are those circRNAs stably existing in exosomes and having high clinical values as novel potential diagnosis and prognosis biomarkers of GC, which have the characteristics of abnormal expression, tissue specificity and development stage specificity. Herein, we briefly summarize the functions and roles and the current research progress of exosomes and exosomal circRNAs in GC with a focus on the potential application for GC progression, diagnosis and prognosis. We also prospected the clinical application of exosomes and exosomal circRNAs in the future.

Tobacco Smoke Plays an Important Role in Initiation and Development of Lung Cancer by Promoting the Characteristics of Cancer Stem Cells.

Lung cancer is one of the most common causes of cancer-related deaths worldwide. Tobacco smoke is the single greatest risk factor of lung cancer. Although enormous progress in understanding the molecular mechanisms by which tobacco smoke leading to lung cancer has been made, the molecular pathogenesis remains largely unclear. Cancer stem cells have been implicated in cancer initiation, development, and drug resistance. In this review, we reviewed the relationship between tobacco smoke and lung cancer, the key role of cancer stem cells in lung cancer and other tumors. More importantly, we elucidate the mechanism of tobacco smoke promoting lung cancer from the perspective of the characteristics of cancer stem cells induced by tobacco smoke.

ß­carotene reverses tobacco smoke­induced gastric EMT via Notch pathway in vivo.

Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial­mesenchymal transition (EMT) has been shown to be associated with the initiation and carcinogenesis of gastric cancer. The role of Notch pathway in regulating tobacco smoke-induced EMT has not been investigated. ß­carotene, a carotenoid present in fruits, vegetables and rice, suppresses cancer progression. In this investigation, we evaluated the regulatory role of Notch pathway in tobacco smoke­mediated gastric EMT and the preventive effect of ß­carotene using a BALB/c mouse smoking model. Exposure of mice to tobacco smoke reduced levels of epithelial markers, while the expression of mesenchymal markers were increased. We further found that Notch pathway modulated tobacco smoke-triggered EMT in the stomach of mice, as evidenced by these findings that tobacco smoke activated Notch activities, and tobacco smoke induced EMT was reversed by blocking Notch activities with FLI­06. Moreover, treatment of ß­carotene prevented tobacco smoke­mediated activation of Notch and EMT changes. Our data suggested that Notch regulate tobacco smoke induced gastric EMT and the protective effects of ß­carotene in vivo. These findings may establish a new mechanism for tobacco smoke-associated gastric tumorigenesis and its chemoprevention.

EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice.

Tobacco smoke is an important risk factor of gastric cancer. Epithelial-mesenchymal transition is a crucial pathophysiological process in cancer development. ERK5 regulation of epithelial-mesenchymal transition may be sensitive to cell types and/or the cellular microenvironment and its role in the epithelial-mesenchymal transition process remain elusive. Epigallocatechin-3-gallate (EGCG) is a promising chemopreventive agent for several types of cancers. In the present study we investigated the regulatory role of ERK5 in tobacco smoke-induced epithelial-mesenchymal transition in the stomach of mice and the preventive effect of EGCG. Exposure of mice to tobacco smoke for 12 weeks reduced expression of epithelial markers E-cadherin, ZO-1, and CK5, while the expression of mesenchymal markers Snail-1, Vimentin, and N-cadherin were increased. Importantly, we demonstrated that ERK5 modulated tobacco smoke-mediated epithelial-mesenchymal transition in mice stomach, as evidenced by the findings that tobacco smoke elevated ERK5 activation, and that tobacco smoke-triggered epithelial-mesenchymal transition was reversed by ERK5 inhibition. Treatment of EGCG (100 mg/kg BW) effectively attenuated tobacco smoke-triggered activation of ERK5 and epithelial-mesenchymal transition alterations in mice stomach. Collectively, these data suggested that ERK5 was required for tobacco smoke-triggered gastric epithelial-mesenchymal transition and that EGCG suppressed ERK5 activation to reverse tobacco smoke-triggered gastric epithelial-mesenchymal transition in BALB/c mice. These findings provide new insights into the mechanism of tobacco smoke-associated gastric tumorigenesis and the chemoprevention of tobacco smoke-associated gastric cancer.