4.7 Article

Carob leaf polyphenols trigger intrinsic apoptotic pathway and induce cell cycle arrest in colon cancer cells

Journal

JOURNAL OF FUNCTIONAL FOODS
Volume 33, Issue -, Pages 112-121

Publisher

ELSEVIER
DOI: 10.1016/j.jff.2017.03.032

Keywords

Carob (Ceratonia siliqua L.); Polyphenols; Colorectal cancer; Caspases; Apoptosis; Cell cycle arrest

Funding

  1. Labex LipSTIC INSERM U1231 University of Burgundy, France
  2. bilateral Franco Algerian collaborative project Tassili [30850QG]

Ask authors/readers for more resources

Chemoprevention of Colorectal cancer (CRC) is the major concern for improving public health. We investigated the protective effects of carob, Ceratonia siliqua L, leaf polyphenols (CLP) against CRC. Phenolic content analysis showed that CLP is enriched with gallic acid and m-coumaric acid. We observed that CLP exerted a dose dependent cytotoxic effect through the induction of apoptosis on CRC cell lines, with an IC50 around 20 mu g/mL CLP induced intrinsic apoptotic pathway through the caspase-9 activation and PARP cleavage in HCT-116 and CT-26 cells. Moreover, CLP induced cell cycle arrest in the G1 phase through p53 activation. Gallic acid and m-coumaric acid exerted similar effect of CLP but at higher concentration to that expected to be present in CLP, suggesting the synergistic effect between polyphenols in CLP activity. Interestingly, the carob leaf infusion reduced CT-26 tumour growth in BALB/c mice. This study suggests that CLP can be used for the prevention of CRC. (C) 2017 Elsevier Ltd. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Review Pharmacology & Pharmacy

Can the hyperthermia-mediated heat shock factor/heat shock protein 70 pathway dampen the cytokine storm during SARS-CoV-2 infection?

Cedric Rebe, Francois Ghiringhelli, Carmen Garrido

Summary: This study analyzes the mechanism involved in the hyperthermia-mediated heat shock factors/heat shock proteins70 pathway, which may provide a new treatment approach for SARS-CoV-2 infection.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Article Oncology

The Tumor Microenvironment Impairs Th1 IFNγ Secretion through Alternative Splicing Modifications of Irf1 Pre-mRNA

Antoine Bernard, Christophe Hibos, Corentin Richard, Etienne Viltard, Sandy Chevrier, Sophie Lemoine, Josephine Melin, Etienne Humblin, Romain Mary, Theo Accogli, Fanny Chalmin, Melanie Bruchard, Paul Peixoto, Eric Hervouet, Lionel Apetoh, Francois Ghiringhelli, Frederique Vegran, Romain Boidot

Summary: The tumor microenvironment (TME) influences immune cell activity by increasing alternative splicing events, leading to the expression of IRF1 Delta 7 in Th1 cells and subsequently decreasing IFN gamma secretion. Inhibiting the expression of IRF1 Delta 7 could enhance Th1 antitumor responses.

CANCER IMMUNOLOGY RESEARCH (2021)

Review Immunology

Harnessing TH9 cells in cancer immunotherapy

Isis Benoit-Lizon, Lionel Apetoh

Summary: CD4 T cell effector subsets have a significant impact on cancer progression and the efficacy of immune checkpoint inhibitors. T(H)9 cells have shown superior antimelanoma activity, but further research is needed to understand their mechanisms and potential in treating other types of cancer.

SEMINARS IN IMMUNOLOGY (2021)

Article Oncology

MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells

Emeric Limagne, Lisa Nuttin, Marion Thibaudin, Elise Jacquin, Romain Aucagne, Marjorie Bon, Solene Revy, Robby Barnestein, Elise Ballot, Caroline Truntzer, Valentin Derangere, Jean-David Fumet, Charlene Latour, Cedric Rebe, Pierre-Simon Bellaye, Coureche-Guillaume Kaderbhai, Aodrenn Spill, Bertrand Collin, Mary B. Callanan, Aurelie Lagrange, Laure Favier, Bruno Coudert, Laurent Arnould, Sylvain Ladoire, Bertrand Routy, Philippe Joubert, Francois Ghiringhelli

Summary: Chemotherapy combined with MEK inhibitor enhances the sensitivity of lung cancer cells to immune checkpoint inhibitors by inducing CXCL10 expression and CD8(+) T cell recruitment. The study also highlights the role of TLR9- and OPTN-dependent mitophagy in enhancing the efficacy of chemoimmunotherapy.

CANCER CELL (2022)

Article Immunology

Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses

Melanie Bruchard, Mannon Geindreau, Anais Perrichet, Caroline Truntzer, Elise Ballot, Romain Boidot, Cindy Racoeur, Emilie Barsac, Fanny Chalmin, Christophe Hibos, Thomas Baranek, Christophe Paget, Bernhard Ryffel, Cedric Rebe, Catherine Paul, Frederique Vegran, Francois Ghiringhelli

Summary: This study reveals the essential function of type 3 innate lymphoid cells (ILC3s) in recruiting T cells to the tumor microenvironment and enhancing antitumor immune responses.

NATURE IMMUNOLOGY (2022)

Article Oncology

CD4 T cell-intrinsic STING signaling controls the differentiation and effector functions of TH1 and TH9 cells

Isis Benoit-Lizon, Elise Jacquin, Thaiz Rivera Vargas, Corentin Richard, Aurelie Roussey, Ludivine Dal Zuffo, Tiffany Martin, Andrea Melis, Daria Vinokurova, Sayyed Hamed Shahoei, Alvaro Baeza Garcia, Cassandre Pignol, Stephane Giorgiutti, Raphael Carapito, Romain Boidot, Frederique Vegran, Richard A. Flavell, Bernhard Ryffel, Eric R. Nelson, Pauline Soulas-Sprauel, Toby Lawrence, Lionel Apetoh

Summary: Activation of STING signaling enhances the differentiation and antitumor functions of T(H)1 and T(H)9 cells by increasing their production of IFN-gamma and interleukin-9, respectively. IRF3 and IFNARs are required for the enhancement of T(H)1 cell differentiation, while mTOR signaling is implicated in T(H)9 cell differentiation in response to STING activation. STING activation boosts the antitumor activity of T(H)1 and T(H)9 cells through their cytokine production, and enhances the efficacy of T(H)9 cells in adoptive transfer against melanoma.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

Article Allergy

NLRP6 negatively regulates type 2 immune responses in mice

Pauline Chenuet, Quentin Marquant, Louis Fauconnier, Ali Youness, Manon Mellier, Tiffany Marchiol, Nathalie Rouxel, Yasmine Messaoud-Nacer, Isabelle Maillet, Aurelie Ledru, Valerie F. J. Quesniaux, Bernhard Ryffel, William Horsnell, Frederique Vegran, Lionel Apetoh, Dieudonnee Togbe

Summary: This study identifies NLRP6 as a negative regulator of type 2 immune responses, highlighting its importance in preventing lung inflammation.

ALLERGY (2022)

Article Oncology

Hematopoietic Prostaglandin D2 Synthase Controls Tfh/Th2 Communication and Limits Tfh Antitumor Effects

Romain Mary, Fanny Chalmin, Theo Accogli, Melanie Bruchard, Christophe Hibos, Josephine Melin, Caroline Truntzer, Emeric Limagne, Valentin Derangere, Marion Thibaudin, Etienne Humblin, Romain Boidot, Sandy Chevrier, Laurent Arnould, Corentin Richard, Quentin Klopfenstein, Antoine Bernard, Yoshihiro Urade, James A. Harker, Lionel Apetoh, Francois Ghiringhelli, Frederique Vegran

Summary: The interaction between T follicular helper (Tfh) cells and Th2 cells through PGD(2) promotes tumor growth, indicating the significant role of Tfh/Th2 cell crosstalk in tumor progression.

CANCER IMMUNOLOGY RESEARCH (2022)

Article Cell Biology

Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors

Trinh-Le-Vi Kieu, Lea Pierre, Valentin Derangere, Sabrina Perrey, Caroline Truntzer, Antoine Jalil, Sebastien Causse, Emma Groetz, Adelie Dumont, Laura Guyard, Laurent Arnould, Jean-Paul Pais de Barros, Lionel Apetoh, Cedric Rebe, Emeric Limagne, Tony Jourdan, Laurent Demizieux, David Masson, Charles Thomas, Francois Ghiringhelli, Mickael Rialland

Summary: Metastatic breast cancer cannot be cured. Elovl5, a protein involved in fatty acid metabolism, is found to be downregulated in breast cancer tumors compared to normal breast tissues. Low expression of Elovl5 is associated with worse prognosis in ER+ breast cancer patients, especially those with lymph node metastases. Decreased Elovl5 expression limits breast cancer cell proliferation but promotes EMT, cell invasion, and lung metastases in murine breast cancer models. The loss of Elovl5 expression induces upregulation of TGF-beta receptors via lipid droplet accumulation, leading to increased cell invasion and lung metastasis. Inhibition of TGF-beta receptors restores proliferation and reduces invasion in low Elovl5 expressing cancer cells. Inhibition of lipid droplet formation reverses the effects triggered by Elovl5 knockdown. Elovl5 is identified as a predictive biomarker for metastatic ER+ breast cancer.

CELL DEATH & DISEASE (2022)

Review Pharmacology & Pharmacy

New Insights Into the Anticancer Effects of p-Coumaric Acid: Focus on Colorectal Cancer

Wafaa Tehami, Abdelhafid Nani, Naim A. Khan, Aziz Hichami

Summary: Colorectal cancer is the second most deadly cancer in the world, and diet plays a significant role in its prevention. Polyphenols, especially p-Coumaric acid, have been gaining attention for their potential anticancer effects. This review provides an overview of p-Coumaric acid's bioavailability and its mechanisms of action against colorectal cancer, including anti-inflammatory and antioxidant properties, induction of apoptosis, cell cycle blockade, and impact on clonogenicity and multidrug resistance.

DOSE-RESPONSE (2023)

Review Cell Biology

Tumor Immunogenic Cell Death as a Mediator of Intratumor CD8 T-Cell Recruitment

Nicolas Roussot, Francois Ghiringhelli, Cedric Rebe

Summary: The success of anticancer treatments depends on the ability of dying cancer cells under chemotherapy or physical stress to activate immune cells and stimulate an antitumor response. This can be achieved through the release of danger-associated molecular patterns (DAMPs) and the recruitment of CD8 T cells. However, the effectiveness of immune checkpoint blockers in reversing T-cell exhaustion is dependent on the recruitment of CD8 T cells within the tumor. Chemokines play a crucial role in CD8 T-cell recruitment. This review aims to explore the role of chemokines released during immunogenic cell death (ICD) in CD8 T-cell recruitment and antitumor response, as well as their potential clinical applications.

CELLS (2022)

Review Biochemistry & Molecular Biology

The Emerging Role of IL-9 in the Anticancer Effects of Anti-PD-1 Therapy

Daria Vinokurova, Lionel Apetoh

Summary: PD-1 blockade rescues failing anticancer immune responses and IL-9 plays an important role in the efficacy of this therapy in both mice and humans. IL-9 can synergize with anti-PD-1 therapy in eliciting anticancer responses. Host factors such as the microbiota and TGF beta in the tumor microenvironment also contribute to the regulation of IL-9 secretion and anti-PD-1 treatment efficacy.

BIOMOLECULES (2023)

Review Nutrition & Dietetics

Targeting inflammasome pathway by polyphenols as a strategy for pancreatitis, gastrointestinal and liver diseases management: an updated review

Abdelhafid Nani, Wafaa Tehami

Summary: Obesity, pancreatitis, cardiovascular, gastrointestinal, and liver diseases are associated with the Western lifestyle, characterized by unhealthy food consumption and lack of physical activity. Inflammasomes, which mediate inflammatory pathways, are affected by dietary habits, but dietary polyphenols can effectively regulate their dysfunction. Flavonoid and non-flavonoid polyphenols maintain intestinal balance, inhibit the NLRP3 inflammasome pathway, and restore redox status through the Nrf2/HO-1 signaling pathway, resulting in decreased levels of pro-inflammatory cytokines.

FRONTIERS IN NUTRITION (2023)

Review Cell Biology

STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer

Fabian Richter, Christophe Paget, Lionel Apetoh

Summary: Adoptive cell therapy (ACT) is effective in treating hematopoietic cancers but not solid tumors. The activation of the STING signaling pathway has been shown to enhance the anticancer efficacy of ACT by triggering dendritic cell activation and immune responses, preventing tumor escape, and improving T cell function in the tumor microenvironment.

CELL STRESS (2023)

Review Medicine, General & Internal

STING signaling in T cells: Relevance in cancer immunotherapy

L. Apetoh

Summary: The use of immune check-point inhibitors in cancer immunotherapy has led to significant achievements, demonstrating the potential of immune cells in fighting cancer. However, many patients do not respond to this treatment, highlighting the need for alternative immunotherapy strategies. The STING protein, known for its role in antiviral defense, has emerged as a promising therapeutic target in oncology and is currently being investigated in clinical trials. While the activation of STING in dendritic cells triggers immune responses, its impact on T cell function remains unclear. This review explores the molecular mechanisms of STING activation in T cells and its implications for the development of cancer immunotherapy strategies.

BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE (2022)

No Data Available