Acute inflammation is a key component of the immune system’s response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, which is involved in the development of many diseases, including cancer. Nowadays, the need to find new potential therapeutic compounds has raised the worldwide scientific interest to study the marine environment. Specifically, microalgae are considered rich sources of bioactive molecules, such as carotenoids, which are natural isoprenoid pigments with important beneficial effects for health due to their biological activities. Carotenoids are essential nutrients for mammals, but they are unable to synthesize them; instead, a dietary intake of these compounds is required. Carotenoids are classified as carotenes (hydrocarbon carotenoids), such as α- and β-carotene, and xanthophylls (oxygenate derivatives) including zeaxanthin, astaxanthin, fucoxanthin, lutein, α- and β-cryptoxanthin, and canthaxanthin. This review summarizes the present up-to-date knowledge of the anti-inflammatory and anticancer activities of microalgal carotenoids both in vitro and in vivo, as well as the latest status of human studies for their potential use in prevention and treatment of inflammatory diseases and cancer.

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids.

Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial-mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.

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Carotenoids in Cancer Metastasis-Status Quo and Outlook.

Tobacco smoke is a major risk factor for lung cancer. Epithelial‑mesenchymal transition (EMT) is decisive in cancer invasion and metastasis, and therefore promotes cancer progression. Mitogen‑activated protein kinase (MAPK) pathways are implicated in various aspects of cancer development and progression, including the EMT process. The chemopreventive effect of curcumin on carcinogenesis has been reported in vivo and in vitro. The present study investigated tobacco smoke‑induced alterations in the MAPK/activator protein‑1 (AP‑1) pathways, and pulmonary EMT changes in the lungs of mice, and further observed the chemopreventive effect of curcumin. The protein expression levels analyzed by western blot analysis demonstrated that 12 weeks of tobacco smoke exposure activated extracellular‑signal‑regulated kinase (ERK) 1/2, c‑Jun N‑terminal kinase (JNK) and p38 MAPK pathways, in addition to AP‑1, in the lungs of mice, while reducing the activation of ERK5/MAPK pathways. The results also indicated that the mRNA and protein levels of the epithelial markers E‑cadherin and zona occludens‑1 were reduced following tobacco smoke exposure. Conversely, the expression levels of mRNA and protein for the mesenchymal markers vimentin and N‑cadherin were increased. Curcumin treatment inhibited tobacco smoke‑induced MAPK/AP‑1 activation, including ERK1/2, JNK and p38 MAPK pathways, and AP‑1 proteins, and reversed EMT alterations in lung tissue. The results of the present study provide new insights into the molecular mechanisms of tobacco smoke‑associated lung cancer and may open up new avenues in the search for potential therapeutic targets in lung tumorigenesis.

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Curcumin reverses tobacco smoke‑induced epithelial‑mesenchymal transition by suppressing the MAPK pathway in the lungs of mice.

Dietary phytochemicals in the regulation of epithelial to mesenchymal transition and associated enzymes: A promising anticancer therapeutic approach.

Beta-carotene is an important natural pigment that is very beneficial to human health. It is widely found in vegetables and fruits. The three main functions are antioxidant effects, cell gap junction-related functions and immune-related functions. Because of its diverse functions, beta-carotene is believed to prevent and treat many chronic diseases. Gastric cancer is one of the most important diseases it can treat. Gastric cancer is a type of cancer with a high incidence. Its etiology varies, and the pathogenesis is complex. Gastric cancer seriously affects human health. The role of beta-carotene, a natural nutrient, in gastric cancer has been explored by many researchers, including molecular mechanisms and epidemiological studies. Molecular studies have mainly focused on oxidative stress, cell cycle, signal transduction pathways and immune-related mechanisms of beta-carotene in gastric cancer. Many epidemiological surveys and cohort studies of patients with gastric cancer have been conducted, and the results of these epidemiological studies vary due to the use of different research methods and analysis of different regions. This paper will summarize the results of these studies, mainly in terms of molecular mechanisms and epidemiological research results, which will provide a systematic basis for future studies of the treatment and prognosis of gastric cancer. This paper will help researchers identify new research directions.

Beta-carotene and its protective effect on gastric cancer

Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial‑mesenchymal 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. β‑carotene, a carotenoid present in fruits, vegetables and rice, suppresses cancer progression. In this investigation, we evaluated the regulatory role of Notch pathway in tobacco smoke‑mediated gastric EMT and the preventive effect of β‑carotene 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 FLI‑06. Moreover, treatment of β‑carotene prevented tobacco smoke‑mediated activation of Notch and EMT changes. Our data suggested that Notch regulate tobacco smoke induced gastric EMT and the protective effects of β‑carotene in vivo. These findings may establish a new mechanism for tobacco smoke-associated gastric tumorigenesis and its chemoprevention.

/pdf/b-carotene-reverses-tobacco-smoke-induced-gastric-emt-via-1cvt0dr8pa.pdf

β‑carotene reverses tobacco smoke‑induced gastric EMT via Notch pathway in vivo.

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.

/pdf/egcg-suppresses-erk5-activation-to-reverse-tobacco-smoke-2p1s9qozc7.pdf

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

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.

/pdf/tobacco-smoke-plays-an-important-role-in-initiation-and-3vdbsl45a9.pdf

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

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.

/pdf/role-of-ferroptosis-and-ferroptosis-related-non-coding-rnas-2x842tyj.pdf

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

/pdf/exosomes-and-exosomal-circrnas-the-rising-stars-in-the-4tegg2voqk.pdf

Longtao Jin

Papers

β‑carotene reverses tobacco smoke‑induced gastric EMT via Notch pathway in vivo.

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

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

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

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