International Journal of Molecular Sciences

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17 pages, 3741 KiB

Open AccessArticle

Protective Effect of Limosilactobacillus fermentum ME-3 against the Increase in Paracellular Permeability Induced by Chemotherapy or Inflammatory Conditions in Caco-2 Cell Models

by Alex De Gregorio, Annalucia Serafino, Ewa Krystyna Krasnowska, Fabiana Superti, Maria Rosa Di Fazio, Maria Pia Fuggetta, Ivano Hammarberg Ferri and Carla Fiorentini

Int. J. Mol. Sci. 2023, 24(7), 6225; https://doi.org/10.3390/ijms24076225 - 25 Mar 2023

Cited by 3 | Viewed by 2479

Abstract

Chemotherapy- or inflammation-induced increase in intestinal permeability represents a severe element in disease evolution in patients suffering from colorectal cancer and gut inflammatory conditions. Emerging data strongly support the gut microbiota’s role in preserving intestinal barrier integrity, whilst both chemotherapy and gut inflammation [...] Read more.

Chemotherapy- or inflammation-induced increase in intestinal permeability represents a severe element in disease evolution in patients suffering from colorectal cancer and gut inflammatory conditions. Emerging data strongly support the gut microbiota’s role in preserving intestinal barrier integrity, whilst both chemotherapy and gut inflammation alter microbiota composition. Some probiotics might have a strong re-balancing effect on the gut microbiota, also positively affecting intestinal barrier integrity. In this study, we asked whether Limosilactobacillus fermentum ME-3 can prevent the intestinal paracellular permeability increase caused by the chemotherapeutic drug Irinotecan or by inflammatory stimuli, such as lipopolysaccharide (LPS). As an intestinal barrier model, we used a confluent and polarized Caco-2 cell monolayer and assessed the ME-3-induced effect on paracellular permeability by transepithelial electrical resistance (TEER) and fluorescent-dextran flux assays. The integrity of tight and adherens junctions was examined by confocal microscopy analysis. Transwell co-cultures of Caco-2 cells and U937-derived macrophages were used as models of LPS-induced intestinal inflammation to test the effect of ME-3 on release of the pro-inflammatory cytokines Tumor Necrosis Factor α, Interleukin-6, and Interleukin-8, was measured by ELISA. The results demonstrate that ME-3 prevents the IRI-induced increment in paracellular permeability, possibly by modulating the expression and localization of cell junction components. In addition, ME-3 inhibited both the increase in paracellular permeability and the release of pro-inflammatory cytokines in the co-culture model of LPS-induced inflammation. Our findings sustain the validity of L. fermentum ME-3 as a valuable therapeutic tool for preventing leaky gut syndrome, still currently without an available specific treatment. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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21 pages, 2505 KiB

Open AccessArticle

Cinnamomum zeylanicum Blume Essential Oil Inhibits Metastatic Melanoma Cell Proliferation by Triggering an Incomplete Tumour Cell Stress Response

by Giulia Cappelli, Daniela Giovannini, Laura Vilardo, Annalisa Basso, Ilaria Iannetti, Marianna Massa, Giuseppe Ruberto, Ryan Muir, Carlo Pastore, Igea D’Agnano and Francesca Mariani

Int. J. Mol. Sci. 2023, 24(6), 5698; https://doi.org/10.3390/ijms24065698 - 16 Mar 2023

Cited by 4 | Viewed by 2081

Abstract

Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a C. zeylanicum essential oil (CINN-EO) and assessed its effect on a human [...] Read more.

Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a C. zeylanicum essential oil (CINN-EO) and assessed its effect on a human metastatic melanoma cell line (M14). Human PBMCs and MDMs from healthy donors were used as normal control cells. CINN-EO induced cell growth inhibition, cell cycle perturbation, ROS and Fe(II) increases, and mitochondrial membrane depolarization. To assess whether CINN-EO could affect the stress response, we analysed iron metabolism and stress response gene expression. CINN-EO increased HMOX1, FTH1, SLC7A11, DGKK, and GSR expression but repressed OXR1, SOD3, Tf, and TfR1 expression. HMOX1, Fe(II), and ROS increases are associated with ferroptosis, which can be reversed by SnPPIX, an HMOX1 inhibitor. Indeed, our data demonstrated that SnPPIX significantly attenuated the inhibition of cell proliferation, suggesting that the inhibition of cell proliferation induced by CINN-EO could be related to ferroptosis. Concurrent treatment with CINN-EO enhanced the anti-melanoma effect of two conventional antineoplastic drugs: the mitochondria-targeting tamoxifen and the anti-BRAF dabrafenib. We demonstrate that CINN-EO-mediated induction of an incomplete stress response specifically in cancer cells affects the proliferation of melanoma cells and can enhance drug cytotoxicity. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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16 pages, 2748 KiB

Open AccessArticle

Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model

by Alex De Gregorio, Ewa Krystyna Krasnowska, Manuela Zonfrillo, Giampietro Ravagnan, Valentina Bordignon, Enzo Bonmassar and Maria Pia Fuggetta

Int. J. Mol. Sci. 2022, 23(15), 8442; https://doi.org/10.3390/ijms23158442 - 29 Jul 2022

Cited by 1 | Viewed by 1937

Abstract

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and [...] Read more.

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-β-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. The results showed that PD alone or in combination with MNC exerts antiproliferative and proapoptotic effects on cancer cells, inhibits the production of the immunosuppressive cytokine IL-10 and of the proinflammatory cytokines upregulated by LPS, and reduces E-selectin and VCAM-1 on endothelial cells. These data provide preclinical support to the hypothesis that PD could be of potential benefit as a therapeutic adjuvant in colon cancer treatment and prevention. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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Review

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19 pages, 1799 KiB

Open AccessReview

Efficacy of Essential Oils in Relieving Cancer Pain: A Systematic Review and Meta-Analysis

by Maria Tiziana Corasaniti, Giacinto Bagetta, Luigi Antonio Morrone, Paolo Tonin, Kengo Hamamura, Takafumi Hayashi, Francesca Guida, Sabatino Maione and Damiana Scuteri

Int. J. Mol. Sci. 2023, 24(8), 7085; https://doi.org/10.3390/ijms24087085 - 11 Apr 2023

Cited by 4 | Viewed by 4417

Abstract

Over 80% of patients affected by cancer develops cancer-related pain, one of the most feared consequences because of its intractable nature, particularly in the terminal stage of the disease. Recent evidence-based recommendations on integrative medicine for the management of cancer pain underline the [...] Read more.

Over 80% of patients affected by cancer develops cancer-related pain, one of the most feared consequences because of its intractable nature, particularly in the terminal stage of the disease. Recent evidence-based recommendations on integrative medicine for the management of cancer pain underline the role of natural products. The present systematic review and meta-analysis aims at appraising for the first time the efficacy of aromatherapy in cancer pain in clinical studies with different design according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieves 1002 total records. Twelve studies are included and six are eligible for meta-analysis. The present study demonstrates significant efficacy of the use of essential oils in the reduction of the intensity of pain associated with cancer (p < 0.00001), highlighting the need for earlier, more homogeneous, and appropriately designed clinical trials. Good certainty body of evidence is needed for effective and safe management of cancer-related pain using essential oils by establishment of a step-by-step preclinical-to-clinical pathway to provide a rational basis for clinical use in integrative oncology. PROSPERO registration: CRD42023393182. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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15 pages, 1226 KiB

Open AccessReview

Improving Whole Tomato Transformation for Prostate Health: Benign Prostate Hypertrophy as an Exploratory Model

by Pier Giorgio Natali, Mauro Piantelli, Marco Minacori, Margherita Eufemi and Luisa Imberti

Int. J. Mol. Sci. 2023, 24(6), 5795; https://doi.org/10.3390/ijms24065795 - 17 Mar 2023

Cited by 3 | Viewed by 2391

Abstract

It is well-established that the beneficial properties of single phytonutrients can be better attained when they are taken with the complex of the molecules present in their natural milieu. Tomato, the fruit providing the most comprehensive complex of prostate-health-preserving micronutrients, has been shown [...] Read more.

It is well-established that the beneficial properties of single phytonutrients can be better attained when they are taken with the complex of the molecules present in their natural milieu. Tomato, the fruit providing the most comprehensive complex of prostate-health-preserving micronutrients, has been shown to be superior to its single-nutrient counterparts in decreasing the incidence of age-related prostate diseases. Herein, we describe a novel tomato food supplement enriched with olive polyphenols, containing cis-lycopene concentrations far exceeding those present in industry-produced tomato commodities. The supplement, endowed with antioxidant activity comparable to that of N-acetylcysteine, significantly reduced, in experimental animals, the blood levels of prostate-cancer-promoting cytokines. In prospective, randomized, double-blinded, placebo-controlled studies performed on patients affected by benign prostatic hyperplasia, its uptake significantly improved urinary symptoms and quality of life. Therefore, this supplement can complement and, in some cases, be an alternative to current benign prostatic hyperplasia management. Furthermore, the product suppressed carcinogenesis in the TRAMP mouse model of human prostate cancer and interfered with prostate cancer molecular signaling. Thus, it may offer a step forward in exploring the potential of tomato consumption to delay or prevent the onset of age-related prostate diseases in high-risk individuals. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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14 pages, 1684 KiB

Open AccessReview

Targeting Gut Microbiota in Cancer Cachexia: Towards New Treatment Options

by Concetta Panebianco, Annacandida Villani, Adele Potenza, Enrica Favaro, Concetta Finocchiaro, Francesco Perri and Valerio Pazienza

Int. J. Mol. Sci. 2023, 24(3), 1849; https://doi.org/10.3390/ijms24031849 - 17 Jan 2023

Cited by 9 | Viewed by 4564

Abstract

Cancer cachexia is a complex multifactorial syndrome whose hallmarks are weight loss due to the wasting of muscle tissue with or without the loss of adipose tissue, anorexia, systemic inflammation, and multi-organ metabolic alterations, which negatively impact patients’ response to anticancer treatments, quality [...] Read more.

Cancer cachexia is a complex multifactorial syndrome whose hallmarks are weight loss due to the wasting of muscle tissue with or without the loss of adipose tissue, anorexia, systemic inflammation, and multi-organ metabolic alterations, which negatively impact patients’ response to anticancer treatments, quality of life, and overall survival. Despite its clinical relevance, cancer cachexia often remains an underestimated complication due to the lack of rigorous diagnostic and therapeutic pathways. A number of studies have shown alterations in gut microbiota diversity and composition in association with cancer cachexia markers and symptoms, thus supporting a central role for dysbiosis in the pathogenesis of this syndrome. Different tools of microbiota manipulation, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been investigated, demonstrating encouraging improvements in cachexia outcomes. Albeit pioneering, these studies pave the way for future research with the aim of exploring the role of gut microbiota in cancer cachexia more deeply and setting up effective microbiota-targeting interventions to be translated into clinical practice. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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23 pages, 553 KiB

Open AccessReview

Integrative Hematology: State of the Art

by Francesca Andreazzoli and Massimo Bonucci

Int. J. Mol. Sci. 2023, 24(2), 1732; https://doi.org/10.3390/ijms24021732 - 15 Jan 2023

Cited by 1 | Viewed by 3207

Abstract

Blood cancers are a group of diseases with thus far frequently poor prognosis. Although many new drugs, including target therapies, have been developed in recent years, there is still a need to expand our therapeutic armamentarium to better deal with these diseases. Integrative [...] Read more.

Blood cancers are a group of diseases with thus far frequently poor prognosis. Although many new drugs, including target therapies, have been developed in recent years, there is still a need to expand our therapeutic armamentarium to better deal with these diseases. Integrative hematology was conceived as a discipline that enriches the patient’s therapeutic possibilities with the use of supplements, vitamins and a nutritional approach aiming at improving the response to therapies and the clinical outcome. We will analyze the substances that have proved most useful in preclinical and clinical studies in some of the most frequent blood diseases or in those where these studies are more numerous; the importance of the nutritional approach and the role of the intestinal microbiota will also be emphasized. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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18 pages, 809 KiB

Open AccessReview

Role of the Microbiota in Lung Cancer: Insights on Prevention and Treatment

by Federica Pizzo, Zaira Maroccia, Ivano Hammarberg Ferri and Carla Fiorentini

Int. J. Mol. Sci. 2022, 23(11), 6138; https://doi.org/10.3390/ijms23116138 - 30 May 2022

Cited by 17 | Viewed by 3978

Abstract

The microbiota is increasingly recognized as a critical player in cancer onset and progression and response to cancer chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world’s deadliest cancers. [...] Read more.

The microbiota is increasingly recognized as a critical player in cancer onset and progression and response to cancer chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world’s deadliest cancers. However, the mechanisms by which the microbiota can impact this type of cancer and patient survival and response to treatments remain poorly investigated. In this review, the peculiarities of the gut and lung microbial ecosystems have been highlighted, and recent findings illustrating the possible mechanisms underlying the microbiota–lung cancer interaction and the host immune response have been discussed. In addition, the mucosal immune system has been identified as a crucial communication frame to ease interactive dynamics between the immune system and the microbiota. Finally, the use of specific next-generation intestinal probiotic strains in counteracting airway diseases has been evaluated. We believe that restoring homeostasis and the balance of bacterial microflora should become part of the routine of integrated cancer interventions, using probiotics, prebiotics, and postbiotics, and promoting a healthy diet and lifestyle. Full article

(This article belongs to the Special Issue Integrative Oncology: From the Lab to New Therapeutic Possibilities)

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