Bertrand Liagre

• Professor, PhD
• Head of Department at Faculté de Pharmacie

Starting from purpurin-18, a stable purpurin-18 imide derivative with intensive absorption in the near infrared has been synthesized. The opening of the exocycle anhydride by a primary alky-lamine bearing an adamantyl group, allows after cyclization the formation of an imide function. This reaction led to the purpurinimide adamantane derivative (PI...

Photodynamic therapy (PDT) has emerged as a promising and evolving modality in cancer treatment leveraging light-sensitive compounds known as photosensitizers to selectively induce cell death in malignant tissues through the generation of reactive oxygen species (ROS). This review delves into the intricate mechanisms of PDT highlighting the pivotal...

Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin's clinical application. Nanotechnology offers a viable solution to the...

Citation: Ghaddar, S.; Pinon, A.; Gallardo-Villagran, M.; Massoud, J.; Ouk, C.; Carrion, C.; Diab-Assaf, M.; Therrien, B.; Liagre, B. Photodynamic Therapy against Colorectal Cancer Using Porphin-Loaded Arene Ruthenium Cages. Int. J. Mol. Sci. 2024, 25, 10847. https://doi. Abstract: Colorectal cancer (CRC) is the third most common cancer in the worl...

Photodynamic therapy (PDT) is a clinically approved, non-invasive therapy currently used for several solid tumors, triggering cell death through the generation of reactive oxygen species (ROS). However, the hydrophobic nature of most of the photosensitizers used, such as chlorins, limits the overall effectiveness of PDT. To address this limitation,...

Photodynamic therapy (PDT) is a clinically approved non-invasive therapy currently used for several solid tumors, triggering cell death through the generation of reactive oxygen species (ROS). However, the hydrophobic nature of most of the photosensitizers (PSs) used, such as chlorins, limits the overall effectiveness of PDT. To address this limita...

In the context of designing innovative anticancer agents, the synthesis of a series of chalcones bearing a 3,4,5-trimethoxylated A ring and a variety of B rings, including phenols and original heterocycles such as chromones, was conducted. For this end, Claisen-Schmidt condensation was performed in basic or acidic conditions between the common star...

Citation: Makhloufi, H.; Pinon, A.; Champavier, Y.; Saliba, J.; Millot, M.; Fruitier-Arnaudin, I.; Liagre, B.; Chemin, G.; Mambu, L. In Vitro Antiproliferative Activity of Echinulin Derivatives from Endolichenic Fungus Aspergillus sp. against Colorectal Cancer. Molecules 2024, 29, 4117. https://doi. Abstract: The endolichenic fungus Aspergillus sp....

Aiming to create an innovative series of anti‐colorectal cancer agents, we designed in this work hybrid triarylmethane compounds. Three hybrid triarylmethanes and their corresponding N‐oxide analogues were successfully synthesized using an efficient procedure that involved connecting two triarylmethane molecules, through mono‐, bi‐, and triethylene...

In this study, dinuclear and tetranuclear arene ruthenium porphyrins were synthesized and assessed for their potential as photosensitizers (PSs) in photodynamic therapy (PDT) using the Colo205 colon cancer cell line as a model system. Reactive oxygen species (ROS) production, cellular uptake, impact on cell viability, and mechanisms of cell death i...

Triarylmethanes and triazoles constituted privileged structures extensively used in drug discovery programs. In this work, 12 novel triarylmethanes linked to a triazole ring were designed, synthetized, and chemically characterized aiming...

Colon cancer poses a complex and substantial global health challenge, necessitating innovative therapeutic approaches. Chalcones, a versatile class of compounds with diverse pharmacological properties, have emerged as promising candidates for addressing colon cancer. Their ability to modulate pivotal signaling pathways in the development and progre...

Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing...

Treatment regimens are regularly evolving alongside novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of this st...

Simple Summary With 19.3 million new cancer cases worldwide and nearly 10.0 million cancer-related deaths cancer is a global health challenge. Cancer is a disease caused by a variety of factors that lead to uncontrolled cell growth. Cancer chemoprevention using natural or synthetic compounds is a critical strategy to mitigate the impact of cancer o...

Treatment regimens are regularly evolving, together with novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of th...

Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, s...

Simple Summary Conventional therapies for the treatment of colorectal cancer induce several side effects that impact the effectiveness of current therapies as well as the quality of patients’ life. In recent years, natural compounds with anticancer properties have gained attention as potential therapeutic agents for various cancers including colore...

Citation: Wahnou, H.; Youlyouz-Marfak, I.; Liagre, B.; Sol, V.; Oudghiri, M.; Duval, R.E.; Limami, Y. Shining a Light on Prostate Cancer: Photodynamic Therapy and Combination Approaches. Pharmaceutics 2023, 15, 1767. https://doi. Abstract: Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therap...

Caralluma europaea is a medicinal plant used in Moroccan popular medicine, which has been employed as a remedy attributed to its anti-inflammatory, antipyretic, antinociceptive, antidiabetic, neuroprotective, and antiparasitic properties. The aim of the present study was to investigate the antitumor activity of both the methanolic and aqueous extra...

Distinctive structural, chemical, and physical properties make the diarylmethane scaffold an essential constituent of many active biomolecules nowadays used in pharmaceutical, agrochemical, and material sciences. In this work, 33 novel diarylmethane molecules aiming to target colorectal cancer were designed. Two series of functionalized olefinic an...

Low oxygen concentration in solid cancer tumors leads to resistance, especially when dealing with photodynamic therapy (PDT) treatments. In fact, the presence of oxygen is mandatory to obtain an efficient PDT treatment. The synthesis of new oxygen carriers, specifically targeting cancer cells, appears to be an elegant strategy to tackle this issue....

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and one of the main causes of cancer deaths in the global population. First-line treatment usually includes surgical procedures followed by combination chemotherapy. Despite the improvements in CRC treatments, the mortality rate remains very high, leading consequently...

The effect of dimethyl sulfoxide (DMSO) in rheumatoid arthritis (RA) human fibroblast-like synoviocytes (FLSs) has been studied on five different samples harvested from the joints (fingers, hands and pelvis) of five women with RA. At high concentrations (>5%), the presence of DMSO induces the cleavage of caspase-3 and PARP-1, two phenomena associat...

Ruthenium-based assemblies containing tetrapyridylporphyrins (TPyP) in their structure have been evaluated as photosensitizers (PS) to treat rheumatoid arthritis (RA) by photodynamic therapy (PDT). TPyP is useless by itself as a PS due to its low solubility in biological media, however, incorporated in metallacages it can be internalized in cells....

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm...

Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and their special affinity to c...

Four tetrapyridylporphyrin and four dipyridylporphyrin arene ruthenium complexes have been synthesized and characterized. In these complexes, the porphyrin core is either metal-free or occupied by zinc, and the arene ligand of the arene ruthenium units are either the standard methyl-isopropyl-benzene ([Formula: see text]cymene) or the less common p...

Background Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity. Purpose As HCMV infection affects inflammation pathways, especially prostaglandin E2 (PGE2) production via cyclooxygenase 2 enzyme (COX-2), we designed 2'-hydroxycha...

Most photosensitizers (PS) suffer from a lack of water solubility and from a low selectivity toward tumor cells. Delivery systems using nanoparticles make it possible to improve PS water solubility, and also tumor targeting via the enhanced permeability and retention (EPR) effect. Among the organelles, mitochondria are attractive target sites for d...

Natural agents have been used to restart the process of differentiation that is inhibited during leukemic transformation of hematopoietic stem or progenitor cells. Autophagy is a housekeeping pathway that maintains cell homeostasis against stress by recycling macromolecules and organelles and plays an important role in cell differentiation. In the...

The aim of this study was to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. Indeed, it is well-known that polyamine transport system is upregulated in tumor cells. 3’,4,4’,5’-tetramethoxychalcone was selected as parent chalcone since...

The poor solubility of most photosensitizers (PS) hampers their practical use as clinical agents. Conjugation of PS with water‐soluble nanoparticles has been often used to bypass this hurdle. We describe in this study the extraction of glucuronoacetylxylan from chestnut sawdust, the hemisynthesis of pheophorbide‐a (Pha) and its covalent attachment...

Two protoporphyrin IX (PpIX) adamantane derivatives were synthesized and then metallated with zinc. The Zn-PpIX derivatives, exhibiting a high singlet oxygen quantum yield, were tested for their photodynamic activity against the HT-29 cell line. In order to enhance their water-solubility and their cellular bioavailability, these photosensitizers we...

Musculoskeletal diseases often demand a drug treatment at the specific site of injury or defect site. In this context, the use of calcium phosphates is attractive as it allows both the bone substitution and the local delivery of a drug substance. In this work, we present a drug delivery device that combines calcium phosphate bioceramic granules and...

Musculoskeletal diseases often demand a drug treatment at the specific site of injury or defect site. In this context, the use of calcium phosphates is attractive as it allows both the bone substitution and the local delivery of a drug substance. In this work, we present a drug delivery device that combines calcium phosphate bioceramic granules and...

Musculoskeletal diseases often demand a drug treatment at the specific site of injury or defect site. In this context, the use of calcium phosphates is attractive as it allows both the bone substitution and the local delivery of a drug substance. In this work, we present a drug delivery device that combines calcium phosphate bioceramic granules and...

The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in brea...

Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was “caged” by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the ri...

Photodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in...

Aims: Prostate cancer is the most common form of cancer in the male. Epidemiological studies have associated increased cancer incidence with reduced consumption of fruit and vegetables. This study was aimed to investigate the influence of dwarf pomegranate extracts (peel, juice, and seeds oil) on the proliferation and apoptosis of human prostate an...

In traditional medicine, Ficus carica (also known as fig) latex is recognized as a remedy with various therapeutic effects. In the present study we investigated the antitumor activity of Ficus carica extracts and latex. We evaluated the effects of increasing concentrations of Ficus carica extracts and latex on HCT-116 and HT-29 human colorectal cel...

Photodynamic Therapy (PDT) has become one of the most promising treatment against autoimmune diseases, such as rheumatoid arthritis (RA), as well as in the treatment of different types of cancer, since it is a non-invasive method and easy to carry out. The three main ingredients of PDT are light irradiation, oxygen, and a photosensitizer (PS). Ligh...

This paper describes the preparation of two chalcone/β-cyclodextrin/cellulose-nanocrystals complexes and the study of their antiproliferative activities against two colorectal and two prostatic cancer cell lines. The aim of this work was to enhance hydrosolubility of chalcones thanks to the hydrophilic character of cellulose nanocrystals. These lat...

A biological screening of sixteen lichen extracts on human HT-29 colorectal cancer cells, led to the selection of Pleurosticta acetabulum, a lichen widely present in tree barks in Europe. Bioguided purification of the acetonic extract resulted in the isolation of cytochalasin E, a common fungal metabolite. This compound is responsible for the anti-...

Background: Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine T...

Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (...

Increasing incidence and mortality of colorectal cancer brings the necessity to uncover new possibilities in its prevention and treatment. Chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. In this study, we investigated the effects of the synthetic chalcone derivative 3-hydroxy-3',4,4',5'-tetra...

A new anti-cancer drug delivery system, based on gold nanoparticles, has been designed for hydrophobic active compounds. The system is a conjugate of gold/polyethyleneimine (AuNPs/PEI) nanoparticles and sulphated β-cyclodextrin (CD). Anionic cyclodextrin was attached to the positively charged AuNPs/PEI nanoparticles by ionic bonds. Tanshinone IIA a...

The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX‑2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX‑2 (HEL cell line) or not (K562 cell line). Moreover, we ma...

Cap dependent translation is mainly regulated at the level of the eukaryotic initiation factor 4E (eIF4E), the activity of which is controlled by phosphorylation and sequestration by its well established regulator, 4E binding protein 1 (4E-BP1). Both eIF4E and 4E-BP1 have been shown to be involved in the malignant progression of multiple human canc...

Photodynamic therapy (PDT) using porphyrins as photosensitizers, is approved in the clinical treatment of solid tumours. In the laboratory of Natural Substances Of Limoges University (LCSN), a new strategy of targeting tumour cells has been developed. For this purpose, protoporphyrin IX (Pp IX) was vectorised with polyamines such as spermidine, ele...

Prostate cancer is the most common malignant cancer in men and the second leading cause of cancer deaths. Previously, we have shown that 2'-hydroxy-4-methylsulfonylchalcone (RG003) induced apoptosis in prostate cancer cell lines PC-3 and DU145. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent,...

Differentiation therapy is a means to treat cancer and is induced by different agents with low toxicity and more specificity than traditional ones. Diosgenin, a plant steroid, is able to induce megakaryocytic differentiation or apoptosis in human HEL erythroleukemia cells in a dose-dependent manner. However, the exact mechanism by which diosgenin i...

Limited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. In the present study, the apoptotic mechanism of action of RG003 (2'-hydroxy-4-methylsulfonylchalcone) and RG005 (4'-chloro-2'-hydroxy...

Cyclooxygenase-2 (COX-2) has been found to be highly expressed in many types of cancers and to contribute to tumorigenesis via the inhibition of apoptosis, increased angiogenesis and invasiveness. In hematological malignancies, COX-2 expression was found to correlate with poor patient prognosis. However, the exact role of COX-2 expression in these...

Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, w...

One of the hallmarks of cancer is resistance to apoptosis. Elucidating the mechanisms of how cancer cells evade or delay apoptosis should lead to novel therapeutic strategies. Previously, we showed that HT-29 colorectal cancer cells undergoing apoptosis overexpressed cyclooxygenase-2 (COX-2), in a p38 dependent pathway, to delay ursolic acid-induce...

Colorectal cancer is one of the most common cancer types and the third leading cause of cancer-related death in the western world. Generally, colorectal cancers are resistant to anticancer drugs. Several lines of evidence support a critical role for cyclooxygenase-2 (COX-2) during colorectal tumorigenesis and its role in chemoresistance. In this st...

Previously, we demonstrated that diosgenin induced apoptosis in colorectal cancer cell lines HCT-116 and HT-29. HT-29 cells have been reported to be one of the most resistant colorectal cancer cell lines to TRAIL-induced apoptosis. In this study, we investigated the effect of diosgenin on TRAIL-induced apoptosis in HT-29 cells. We showed that diosg...

Differentiation therapy could be one strategy for stopping cancer cell proliferation. A plant steroid, diosgenin, is known to induce megakaryocytic differentiation in human erythroleukemia (HEL) cells. In recent studies, the use of sedimentation field-flow fractionation (SdFFF) allowed the preparation of subpopulations that may differ in regard to...

We studied the relationship between diosgenin-induced apoptosis and arachidonic acid metabolism in two cancer cell lines, the HT-29 and HCT-116. Diosgenin is a steroidal saponin known for its antiproliferative and pro-apoptotic effects on cancer cells. We focused our attention on two enzymes intervening in two different pathways of arachidonic meta...

We studied the relationship between diosgenin-induced apoptosis and arachidonic acid metabolism in two cancer cell lines, the HT-29 and HCT-116. Diosgenin is a steroidal saponin known for its antiproliferative and pro-apoptotic effects on cancer cells. We focused our attention on two enzymes intervening in two different pathways of arachidonic meta...

Classically described as a macroscale size-density based method, Sedimentation field flow fractionation (SdFFF) has been successfully used for cell sorting. The goal of this study was to develop a new SdFFF device for downscale applications, in particular for oncology research to rapidly monitor chemical biological event induction in a cell line. T...

Daphne gnidium L. is a well-known Moroccan plant with cancer-related ethnobotanical use. In order to systematically evaluate its potential activity in breast cancer, four extracts from this plant of different polarity were tested for their antiproliferative effects on MCF-7 cells. The second aspect of this study related to understanding the nature...

Many natural components of plants extract are studied for their beneficial effects on health and particularly on carcinogenesis chemoprevention. In this study, we investigated the effect of citral (3,7-dimethyl-2,6-octadienal), a key component of essential oils extracted from several herbal plants, on the proliferation rate, cell cycle distribution...

Diosgenin is a plant steroid which is able to induce megakaryocytic differentiation of human erythroleukemia (HEL) cells followed by apoptosis at a later stage. Apoptosis markers and phospho-kinases involved during the subsequent apoptosis of megakaryocytes after diosgenin-induced differentiation in these cells were detected using a proteomic appro...

Recently, sedimentation field-flow fractionation (SdFFF) was used to study the specific kinetics of diosgenin-induced apoptosis in K562 cells. Here, we propose a new SdFFF cell separation application in the field of cancer research concerning the correlation between induction of a biological event (i.e. apoptosis) and cell status (i.e. cell cycle p...

Differentiation induction as a therapeutic strategy has, so far, the greatest impact in hematopoietic malignancies, most notably leukemia. Diosgenin is a very interesting natural product because, depending on the specific dose used, its biological effect is very different in HEL (human erythroleukemia) cells. For example, at 10 microM, diosgenin in...

Recently, the use of SdFFF in cancer research has been studied in order to better understand major phenomena implicated in cancer development and therapy: apoptosis and differentiation. In this report, we used SdFFF as a monitoring and cell separation tool to study the kinetics of apoptosis. Incubation of K562 cells with diosgenin, used as cellular...

We conducted our study to assess the antiproliferative and proapoptotic potential of hecogenin and tigogenin, two saponins which are structurally similar to diosgenin. We particularly focused our attention on mitogen-activated protein kinase (MAPK) activation in relation to apoptosis but also with the COX-2 expression and activity. Rheumatoid arthr...

Anti-cancer differentiation therapy could be one strategy to stop cancer cell proliferation. We propose a new sedimentation field flow fractionation (SdFFF) cell separation application in the field of cancer research. It concerns the study of megakaryocytic differentiation processes after a short exposure to an inducting agent (diosgenin). Washout...

In the present study, we investigated the signalling pathways involved in diosgenin-induced apoptosis in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) in vitro with particular interest on Akt and MAPKs activation in relation to arachidonic acid metabolism via COX-2 pathway. MAPK activation was measured by ELISA quantification i...

Rheumatoid arthritis (RA) is characterized by persistent joint synovial tissue inflammation. Leflunomide is an immunomodulatory agent that has been approved for treatment of active RA. In the past few years, uses other than RA treatment have appeared. Leflunomide has been reported to show antitumor potential through inhibition of cancer cell prolif...

Apoptosis is one of the most important phenomena in cell biology. Pre-apoptotic cells, defined as cells engaged in early stages of apoptosis, could be used as a cellular tool to study apoptosis pathways. The human 1547 osteosarcoma cell line and diosgenin (a plant steroid) association was selected as an in vitro cellular apoptosis model. In a previ...

Anticancer differentiation therapy could be one strategy to stop cancer cell proliferation. Human erythroleukemia (HEL) cell line, incubated with 10 microM diosgenin, underwent megakaryocytic differentiation. Thus, the association diosgenin/HEL could be used as a model of chemically induced cellular differentiation and anticancer treatment. The goa...

Megakaryocytopoiesis is characterized by progressive polyploidization and acquisition of megakaryo-cytic markers. MAPK pathways play a key role during megakaryocytic differentiation of megakaryocyte precursors or leukemic cells. Apoptosis is the physiological fate of normal megakaryocyte after differentiation and maturation. The aim of this study w...

Diosgenin is a steroidal sapogenin with antitumor properties. We previously showed that diosgenin induced apoptosis in human erythroleukemia (HEL) cells. In order to elucidate the mechanism of its apoptotic activity, we investigated the effect of diosgenin on nuclear factor-kappaB (NF-kappaB) binding and on three groups of human mitogen-activated p...

Inflammatory cytokines or soluble factors are essential in the pathogenesis of rheumatoid arthritis (RA). Leflunomide is an effective disease modifying antirheumatic drug (DMARD) in RA. The objective of the present study was to evaluate for the first time the effects of A77 1726 on cytokine (interleukin (IL)-8, IL-10, IL-11 secretion and tumor necr...

In this paper, eight natural molecules structurally close to diosgenin (five saponins: diosgenin, hecogenin, tigogenin, sarsasapogenin, smilagenin; two steroidal alkaloids: solasodine, solanidine; one sterol: stigmasterol) have been tested for their biological activities on human 1547 osteosarcoma cells. Differences in activity were studied in term...

To limit or stop cancer spreading, one of the most prevalent strategies is to induce cancer cell death. Differentiation therapy and apoptosis induction are two ways to achieve this goal. Sedimentation field-flow fractionation (SdFFF) has been described as an effective tool for cell separation, respecting integrity and viability. Because SdFFF takes...