In vitro chemopreventive and cytotoxic effects of Amazon mosses Leucobryum martianum (Hornsch.) and Leucobryum laevifolium (Broth) extracts.

Several bioactive compounds, such as polyphenols, demonstrate low toxicity and prominent effects on cancer cells with antioxidant, anti-inflammatory, and antitumor activities. Such compounds can be found in Amazon mosses Leucobryum martianum (Hornsch.) Hampe ex Müll. Hal. (Hornsch.) and Leucobryum laevifolium (Broth). Antimutagenic assay with Salmonella enterica serovar Typhimurium and cytotoxicity with different eukaryotic cell lines were carried out to screen aqueous, hydroalcoholic, and ethanolic extracts of those Amazon mosses for anticancer potential. The results indicate the capacity of all extracts of both mosses to exert chemopreventive effects against 4-nitroquinoline-N-oxide (4NQO) and 2-aminoanthracene (2-AA), which are direct or indirect mutagens. In particular, the ethanolic and aqueous extract from L. martianum. The ethanolic extract from L. martianum induces significant cytotoxicity by mitochondrial metabolism and cell membrane disruption pathways to tumor or non-tumor cells. The aqueous extract from L. martianum showed a mainly cytotoxic response in the HepG2 cells, a human liver carcinoma, reaching ~90% cytotoxicity. The same extract did not induce significant damage to normal liver cells (F C3H cells) by membrane interaction pathway. The selective cytotoxicity in the aqueous extract of L. martianum makes it a candidate against liver cancer. Further studies, including in vivo models, are necessary to validate the efficacy and safety of the aqueous extract of L. martianum.

Applications of Proteomics in Probiotics Having Anticancer and Chemopreventive Properties.

Proteomics has grown in importance in molecular sciences because it gives vital information on protein identification, expression levels, and alteration. Cancer is one of the world's major causes of death and is the major focus of much research. Cancer risk is determined by hereditary variables as well as the body's immunological condition. Probiotics have increasing medical importance due to their therapeutic influence on the human body in the prevention and treatment of numerous chronic illnesses, including cancer, with no adverse effects. Several anticancer, anti-inflammatory, and chemopreventive probiotics are studied using different proteomic approaches like two-dimensional gel electrophoresis, liquid chromatography-mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. To gain relevant information about probiotic characteristics, data from the proteomic analysis are evaluated and processed using bioinformatics pipelines. Proteomic studies showed the significance of different proteomic approaches in characterization, comparing strains, and determination of oxidative stress of different probiotics. Moreover, proteomic approaches identified different proteins that are involved in glucose metabolism and the formation of cell walls or cell membranes, and the differences in the expression of critical enzymes in the HIF-1 signaling pathway, starch, and sucrose metabolism, and other critical metabolic pathways.

Anticancer and chemopreventive potential of Morinda citrifolia L. bioactive compounds: A comprehensive update.

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.

Coffee Bean and Its Chemical Constituent Caffeine and Chlorogenic Acid as Promising Chemoprevention Agents: Updated Biological Studies against Cancer Cells.

Cancer is a complicated and ever-evolving disease that remains a significant global cause of disease and mortality. Its complexity, which is evident at the genetic and phenotypic levels, contributes to its diversity and resistance to treatment. Numerous scientific investigations on human and animal models demonstrate the potential of phytochemicals in cancer prevention. Coffee has been shown to possess potent anti-carcinogenic properties, and studies have documented the consumption of coffee as a beverage reduces the risk of cancer occurrence. The major secondary metabolites of coffee, named caffeine and chlorogenic acid, have been linked to anti-inflammatory and antineoplastic effects through various signaling. In light of this, this review article provides a comprehensive analysis based on studies in anticancer effects of coffee, chlorogenic acid, and caffeine published between 2010 and 2023, sourced from Scopus, Pubmed, and Google Scholar databases. We summarize recent advances and scientific evidence on the association of phytochemicals found in coffee with a special emphasis on their biological activities against cancer and their molecular mechanism deemed potential to be used as a novel therapeutic target for cancer prevention and therapy.

The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review.

Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment.

Comparative Studies of Extracts Obtained from Brassica oleracea L. Plants at Different Stages of Growth by Isolation and Determination of Isothiocyanates: An Assessment of Chemopreventive Properties of Broccoli.

The main goal of this work was to develop analytical procedures for the isolation and determination of selected isothiocyanates. As an example, particularly sulforaphane from plants of the Brassicaceae Burnett or Cruciferae Juss family. The applied methodology was mainly based on classical extraction methods and high-performance liquid chromatography coupled with tandem mass spectrometry. Moreover, the effect of temperature on the release of isothiocyanates from plant cells was considered. The cytotoxic activity of the obtained plant extracts against a selected cancer cell line has also been included. The results allow evaluating the usefulness of obtained plant extracts and raw sprouts regarding their content of isothiocyanates-bioactive compounds with chemopreventive properties.

Salvianolic acid B as a potent nano-agent for enhanced ALA-PDT of oral cancer and leukoplakia cells.

BACKGROUND: Photodynamic therapy (PDT) relies on the light activation of a photosensitizers to generate reactive oxygen species such as singlet oxygen, but its effect on cancer therapy is limited dramatically by hypoxia in the tumor microenvironment. OBJECTIVES: To determine the potential of a nano-photosensitizer loaded salvianolic acid B (SalB) and 5-aminolevulinic acid (ALA) for enhancing the efficacy of PDT in oral squamous cell carcinoma Cal27 cells and leukoplakia Leuk1 cells. RESULTS: Singlet oxygen sensor green (SOSG) assay showed that nano-SalB-ALA generated higher levels of singlet oxygen, compared to nano-SalB and nano-ALA. Cellular uptake assay showed that nano-SalB-ALA effectively absorbed by Leuk1 cells. Importantly, cell counting kit-8 and flow cytometry revealed that PDT with nano-SalB-ALA effectively inhibited the viability and induced the apoptosis of Cal27 and Leuk1 cells, respectively. Moreover, the tumor xenograft study revealed that PDT with nano-SalB-ALA had a stronger inhibitory effect on tumor growth of nude mice, compared to control groups. CONCLUSIONS: The novel photosensitizer nano-SalB-ALA remarkably enhanced the efficacy of PDT by improving singlet oxygen production, inhibiting cell proliferation, promoting cell apoptosis, and suppressing tumor growth. These suggest PDT with nano-SalB-ALA could be a clinically significant and potent treatment for oral cancer and leukoplakia.

Quercetin as a cancer chemopreventive or chemotherapeutic agent: Where we stand.

Quercetin has a wide range of potential health benefits, working as a direct or indirect agent or an adjuvant following different principles. It may be used as a generally useful or exclusive supplement, but also specifically used to treat an acute or chronic condition. Quercetin may work as a cancer chemopreventive and chemotherapeutic agent, because this versatile substance, which owns antioxidant and anti-inflammatory properties, may also kill cancer cells and also holds senolytic properties. While both the specific chemo-preventive or chemotherapeutic uses as a drug need clinical trials, it may be used without any contraindication as a general chemo-preventive supplement.

Potential Chemopreventive Role of Pterostilbene in Its Modulation of the Apoptosis Pathway.

Cancer incidence keeps increasing every year around the world and is one of the leading causes of death worldwide. Cancer has imposed a major burden on the human population, including the deterioration of physical and mental health as well as economic or financial loss among cancer patients. Conventional cancer treatments including chemotherapy, surgery, and radiotherapy have improved the mortality rate. However, conventional treatments have many challenges; for example, drug resistance, side effects, and cancer recurrence. Chemoprevention is one of the promising interventions to reduce the burden of cancer together with cancer treatments and early detection. Pterostilbene is a natural chemopreventive compound with various pharmacological properties such as anti-oxidant, anti-proliferative, and anti-inflammatory properties. Moreover, pterostilbene, due to its potential chemopreventive effect on inducing apoptosis in eliminating the mutated cells or preventing the progression of premalignant cells to cancerous cells, should be explored as a chemopreventive agent. Hence, in the review, we discuss the role of pterostilbene as a chemopreventive agent against various types of cancer via its modulation of the apoptosis pathway at the molecular levels.

Hydroxy Chalcones and Analogs with Chemopreventive Properties.

The aim of this review is to highlight the chemopreventive properties of hydroxy-substituted natural and synthetic chalcones along with a number of their analogs. These products display various biological activities, and have many applications against various diseases. Antioxidant and anti-inflammatory properties of chalcones bearing hydroxy substituents are underlined. The influence of hydroxy substituents located on ring A, B, or both are systematized according to the exhibited biological properties.

Antiproliferative, Antioxidant, Chemopreventive and Antiangiogenic Potential of Chromatographic Fractions from Anemonia sulcata with and without Its Symbiont Symbiodinium in Colorectal Cancer Therapy.

Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progression by creating an energy crisis for preneoplastic cells, resulting in antiproliferative effects. These effects are referred to as chemopreventive effects mediated by an antioxidant mechanism. In addition, antioxidants minimize chemotherapy-induced nonspecific organ toxicity and prolong survival. Antioxidants also support the prooxidant chemistry that demonstrate chemotherapeutic potential, particularly at high or pharmacological doses and trigger OS by promoting free radical production, which is essential for activating cell death pathways. A growing body of evidence also revealed the roles of exogenous antioxidants as adjuvants and their ability to reverse chemoresistance. In this review, we explain the influences of different exogenous and endogenous antioxidants on brain cancers with reference to their chemopreventive and chemotherapeutic roles. The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. Finally, the review hypothesized that both pro- and antioxidant roles are involved in the anticancer mechanisms of the antioxidant molecules by killing neoplastic cells and inhibiting tumor recurrence followed by conventional cancer treatments. The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. Finally, we also mention the influencing factors that regulate the pharmacology of the exogenous antioxidants in brain cancer treatment. In conclusion, to achieve consistent clinical outcomes with antioxidant treatments in brain cancers, rigorous mechanistic studies are required with respect to the types, forms, and stages of brain tumors. The concomitant treatment regimens also need adequate consideration.

Enzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms.

Quercetin and its glycosides, such as isoquercitrin or rutin, are among the most ubiquitous flavonoids present in plants. They possess numerous health-promoting properties, whose applicability is, however, limited by poor water solubility and absorption issues. Enzymatically modified isoquercitrin (EMIQ) is an isoquercitrin derivative obtained from rutin via enzymatic transformations that greatly enhance its bioavailability. Due to advantageous reports on its safety and bioactivity, EMIQ is currently gaining importance as a food additive and a constituent of dietary supplements. This review summarizes the thus-far-conducted investigations into the metabolism, toxicity, biological properties, and molecular mechanisms of EMIQ and presents a comprehensive characterization of this valuable substance, which might represent the future of flavonoid supplementation.

Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis.

BACKGROUND: D-limonene and its derivatives have demonstrated potential chemopreventive and anticancer activity in preclinical and clinical studies. The aim of this scoping review was to assess and critically appraise current literature on the effect of these bioactive citrus peel compounds on breast cancer in human trials and to identify knowledge gaps for exploration in future studies. METHODS: This study followed a scoping review framework. Peer-reviewed journal articles were included if they reported the effect of d-limonene or its derivatives on breast cancer in human subjects. Articles were retrieved from academic databases - PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews - and iteratively through review of bibliographies of relevant manuscripts. Titles and abstracts were appraised against the aforementioned inclusion criteria in a first round of screening. Through consensus meetings and full article review by authors, a final set of studies were selected. Results were reported according to the PRISMA extension for scoping reviews. RESULTS: Our search strategy yielded 367 records. Following screening and adjudication, five articles reporting on phase 1(n = 2), phase 2 (n = 2) and both trial phases (n = 1) were included as the final dataset for this review. Trials evaluating the effect of d-limonene (n = 2) showed it was well tolerated in subjects. One study (n = 43 participants) showed d-limonene concentrated in breast tissue (mean 41.3 µg/g tissue) and reduction in tumor cyclin D1 expression, which is associated with tumor proliferation arrest. This study did not show meaningful change in serum biomarkers associated with breast cancer, except for a statistically significant increase in insulin-like growth factor-1 (IGF-I) levels. While elevation of IGF-I is associated with increased cancer risk, the clinical implication of this study remains uncertain given its short duration. Trials with perillyl alcohol (n = 3) showed low tolerance and no effect on breast cancer. CONCLUSION: This review demonstrated a dearth of clinical studies exploring the effect of d-limonene and its derivatives on breast cancer. Limited literature suggests d-limonene is safe and tolerable in human subjects compared to its derivative, perillyl alcohol. Our review demonstrates the need for additional well-powered placebo-controlled trials that assess d-limonene's efficacy on breast cancer compared to other therapies.

Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review.

Benzyl isothiocyanate (BITC) is one of the common isothiocyanates found in cruciferous vegetables such as broccoli, cabbage or watercress. Preclinical studies report of its effectiveness in the prevention and treatment against several cancers. This review aims to report and discuss findings on anticancer activities of BITC and its modes of action against 14 types of cancer. A literature search was conducted using the keywords "BITC" and "anticancer" from PubMed, Google Scholar and CINAHL Plus to obtain relevant research articles. This review highlights the anticancer efficacy of BITC through modulation of various signaling pathways involved in apoptosis, cell proliferation, cell cycle arrest, metastasis, angiogenesis, autophagy and the effects of BITC in combination with other drugs. With the available pharmacology evidence, we conclude that further studies are needed to validate its effectiveness in humans for further development and translation into prophylaxis or therapy by promoting optimal therapeutic effects and minimizing toxicity in cancer treatment.

Anticancer activity of limonene: A systematic review of target signaling pathways.

Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and limiting tumor growth and angiogenesis in various cancer models. Twenty-six (26) articles were selected based on previously established criteria. Anticancer activity of LIM was related to the inhibition of tumor initiation, growth, and angiogenesis and the induction of cancer cells apoptosis. LIM was able to increase Bax expression, release cytochrome c, and activate the caspase pathway. In addition, LIM increased the expression of p53 and decreased the activity of Ras/Raf/MEK/ERK and PI3K/Akt pathways. LIM also decreased the expression of VEGF and increased the activities of the Man-6-P / IGF2R and TGF-ßIIR receptors. These results highlight LIM as an abundant natural molecule with low toxicity and pleiotropic pharmacological activity in cancer cells, targeting various cell-signaling pathways critically involved in the initiation, growth, and chemoresistance of cancer cells.

Selected Monocyclic Monoterpenes and Their Derivatives as Effective Anticancer Therapeutic Agents.

Terpenes-a diverse group of secondary metabolites-constitute the largest class of natural products abundant in almost every plant species. The properties of concrete terpenes and essential oils have been intensively studied due to their widespread use in the pharmaceutical, food and cosmetics industries. Despite the popularity of these aromatic compounds, their derivatives, terpenoids, are still not comprehensively characterized despite exhibiting potent bioactive properties. This review aims to assess the anticancer properties of selected monoterpenes including carvone, carvacrol, perillyl alcohol, perillaldehyde, limonene, menthol and their derivatives while also evaluating potential applications as novel anticancer treatments. Special attention is paid to functional groups that improve the bioactivity of monoterpene molecules. This review also covers the therapeutic potential of deep eutectic solvents that contain monoterpene substances. Taken together, the literature supports the use of monoterpene derivatives in the development of new alternatives for disease treatment and prevention.

Anti-Allergic Drug Suppressed Pancreatic Carcinogenesis via Down-Regulation of Cellular Proliferation.

Pancreatic cancer is a fatal disease, and thus its chemoprevention is an important issue. Based on the recent report that patients with allergic diseases have a low risk for pancreatic cancer, we examined the potential chemopreventive effect of anti-allergic agents using a hamster pancreatic carcinogenesis model. Among the three anti-allergic drugs administered, montelukast showed a tendency to suppress the incidence of pancreatic cancer. Further animal study revealed a significantly decreased incidence of pancreatic cancer in the high-dose montelukast group compared with controls. The development of the pancreatic intraepithelial neoplasia lesions was also significantly suppressed. The Ki-67 labeling index was significantly lower in pancreatic carcinomas in the high-dose montelukast group than in controls. In vitro experiments revealed that montelukast suppressed proliferation of pancreatic cancer cells in a dose-dependent manner with decreased expression of phospho-ERK1/2. Montelukast induced G1 phase arrest. Conversely, leukotriene D4 (LTD4), an agonist of CYSLTR1, increased cellular proliferation of pancreatic cancer cells with an accumulation of phospho-ERK1/2. In our cohort, pancreatic ductal adenocarcinoma patients with high CYSLTR1 expression showed a significantly unfavorable clinical outcome compared with those with low expression. Our results indicate that montelukast exerts a chemopreventive effect on pancreatic cancer via the LTD4-CYSLTR1 axis and has potential for treatment of pancreatic carcinogenesis.

Lasius fuliginosus Nest Carton as a Source of New Promising Bioactive Extracts with Chemopreventive Potential.

Six new water extracts (E1-E6) were obtained from nest carton produced by jet black ants Lasius fuliginosus and tested for their biochemical and bioactive properties, including antioxidative and anticancer effects. The present study demonstrated significant qualitative and quantitative differences in the content of individual biochemical constituents, as well as bioactive properties between the investigated samples. All tested extracts demonstrated antioxidant properties (determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods), and the highest antioxidative potential was recorded in extracts E1 and E2 (188.96 and 313.67 µg/mL of ascorbic acid equivalent for ABTS and 176.42 and 202.66 µg/mL for DPPH reagent). Furthermore the six extracts exhibited strong inhibitory activity towards human melanoma cells of the A-375 CRL-1619 line in a dose-dependent manner. The most interesting chemopreventive activity was exhibited by extract E2, which inhibited the proliferation of A-375 cells to the greatest extent, while having a minimal effect on Vero cells. The effect on cancer cells has been confirmed using the Electric Cell-substrate Impedance Sensing (ECIS) technique. Significant impedance changes have been detected in A-375 and Vero cells following the administration of extract E2. The obtained results are really promising and constitute the basis for further research on the nest carton of jet black ant.

Regulation of Selenium/Sulfur Interactions to Enhance Chemopreventive Effects: Lessons to Learn from Brassicaceae.

Selenium (Se) is an essential trace element, which represents an integral part of glutathione peroxidase and other selenoproteins involved in the protection of cells against oxidative damage. Selenomethionine (SeMet), selenocysteine (SeCys), and methylselenocysteine (MeSeCys) are the forms of Se that occur in living systems. Se-containing compounds have been found to reduce carcinogenesis of animal models, and dietary supplemental Se might decrease cancer risk. Se is mainly taken up by plant roots in the form of selenate via high-affinity sulfate transporters. Consequently, owing to the chemical similarity between Se and sulfur (S), the availability of S plays a key role in Se accumulation owing to competition effects in absorption, translocation, and assimilation. Moreover, naturally occurring S-containing compounds have proven to exhibit anticancer potential, in addition to other bioactivities. Therefore, it is important to understand the interaction between Se and S, which depends on Se/S ratio in the plant or/and in the growth medium. Brassicaceae (also known as cabbage or mustard family) is an important family of flowering plants that are grown worldwide and have a vital role in agriculture and populations' health. In this review we discuss the distribution and further interactions between S and Se in Brassicaceae and provide several examples of Se or Se/S biofortifications' experiments in brassica vegetables that induced the chemopreventive effects of these crops by enhancing the production of Se- or/and S-containing natural compounds. Extensive further research is required to understand Se/S uptake, translocation, and assimilation and to investigate their potential role in producing anticancer drugs.