-
Biomedicine & Pharmacotherapy =... Jul 2023Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and... (Review)
Review
Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells. This review discusses the potential of curcumin as an antimetastatic agent and describes potential mechanisms of its antimetastatic activity. In addition, possible strategies (curcumin formulation, optimization of the method of administration and modification of its structure motif) to overcome its limitation such as low solubility and bioactivity are also presented. These strategies are discussed in the context of clinical trials and relevant biological studies.
Topics: Humans; Curcumin; Antineoplastic Agents; Neoplasms
PubMed: 37141738
DOI: 10.1016/j.biopha.2023.114758 -
Pharmacology & Therapeutics May 2024Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug... (Review)
Review
Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug discovery, but there is growing recognition of the importance of the more complex orthotopic and metastatic tumour models for understanding both target biology in the correct tissue context, and the impact of the tumour microenvironment and the immune system in responses to treatment. The aim of this review is to highlight the value that orthotopic and metastatic models bring to the study of tumour biology and drug development while pointing out those models that are most likely to be encountered in the literature. Important developments in orthotopic models, such as the increasing use of early passage patient material (PDXs, organoids) and humanised mouse models are discussed, as these approaches have the potential to increase the predictive value of preclinical studies, and ultimately improve the success rate of anticancer drugs in clinical trials.
Topics: Animals; Mice; Humans; Xenograft Model Antitumor Assays; Immune System; Antineoplastic Agents; Neoplasms; Disease Models, Animal; Tumor Microenvironment
PubMed: 38467308
DOI: 10.1016/j.pharmthera.2024.108631 -
Journal of Cancer Research and Clinical... Sep 2023The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the...
PURPOSE
The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the 1.4.5-oxathiazine-4.4-dioxide, known as substance GP-2250, possesses antineoplastic properties as shown on pancreatic carcinoma. This current study aims to gain insights into the structure and activity relationship of a series of different Oxathiazinanes regarding their antineoplastic activity and the potential correlation with antibacterial activity. We investigated the newly synthesized Oxathiazinane derivatives: 2255, 2256, 2287, 2289, 2293 and 2296 in comparison to GP-2250.
METHODS
The antineoplastic effect was evaluated in different cancer entities (breast, skin, pancreas and colon cancer cell lines) by viability, proliferation, and cell migration assays in vitro. Disc diffusion tests were performed on various bacteria strains to examine the antibacterial potential. Additionally, reactive oxygen species (ROS) assays were conducted to investigate mechanistic aspects.
RESULTS
The substances GP-2250, 2293, 2289 and 2296 not only showed antineoplastic activity in four different cancer entities but also antibacterial effects, as tested on multiple bacteria strains including MRSA (Methicillin-resistant Staphylococcus aureus). Furthermore, these substances also induced high ROS levels up to 110% in the treated cancer cell lines compared to untreated control cells. These results indicate a correlation between an antineoplastic capacity and antibacterial properties of these derivatives. Both activities appear to be ROS driven. The Oxathiazinane derivatives 2255, 2256 and 2287 lacked both, antineoplastic and antibacterial activity.
CONCLUSION
Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Reactive Oxygen Species; Microbial Sensitivity Tests; Anti-Bacterial Agents; Bacteria; Antineoplastic Agents
PubMed: 37171614
DOI: 10.1007/s00432-023-04799-8 -
Biomedicine & Pharmacotherapy =... Apr 2024Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions... (Review)
Review
Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, and various types of cancer. Therefore, it is critical to suppress cancer progression and proliferation. Ferroptosis can be triggered in cancer cells and some normal cells by synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or clinical pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, and some have been therapeutically used as dietary additives or pharmaceutical agents against various malignancies. The fact that natural products have multiple targets and minimal side effects has led to notable advances in anticancer research. Research has indicated that ferroptosis can also be induced by natural compounds during cancer treatment. In this review, we focused on the most recent developments in emerging molecular processes and the significance of ferroptosis in cancer. To provide new perspectives on the future development of ferroptosis-related anticancer medications, we also provide a summary of the implications of natural phytochemicals in triggering ferroptosis through ROS production and ferritinophagy induction in a variety of malignancies.
Topics: Humans; Ferroptosis; Reactive Oxygen Species; Iron; Neoplasms; Antineoplastic Agents
PubMed: 38479184
DOI: 10.1016/j.biopha.2024.116363 -
Biomedicine & Pharmacotherapy =... Jul 2023Head and neck squamous cell carcinoma (HNSCC) arises from the interplay of multiple factors, such as smoking, alcohol consumption, and viral infections. Cisplatin-based... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) arises from the interplay of multiple factors, such as smoking, alcohol consumption, and viral infections. Cisplatin-based concurrent radiotherapy regimens represent the first-line treatment for advanced HNSCC cases. However, cisplatin resistance significantly contributes to poor prognoses in HNSCC patients, making it crucial to unravel the underlying mechanisms to overcome this resistance. The complexity of cisplatin resistance in HNSCC involves cancer stem cells, autophagy, epithelial-mesenchymal transition, drug efflux, and metabolic reprogramming. Recent advances in nanodrug delivery systems, combined with existing small-molecule inhibitors and innovative genetic technologies, have opened new therapeutic avenues for addressing cisplatin resistance in HNSCC. This review systematically summarizes research progress from the past five years on cisplatin resistance in HNSCC, with a particular focus on the roles of cancer stem cells and autophagy. Additionally, potential future treatment strategies to overcome cisplatin resistance are discussed, including the targeting of cancer stem cells or autophagy through nanoparticle-based drug delivery systems. Furthermore, the review highlights the prospects and challenges associated with nanodelivery platforms in addressing cisplatin resistance in HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Cisplatin; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Drug Resistance, Neoplasm; Cell Line, Tumor; Antineoplastic Agents
PubMed: 37137185
DOI: 10.1016/j.biopha.2023.114778 -
International Journal of Molecular... Jul 2023Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited... (Review)
Review
Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited translational significance, animal ethics, and inter-species physiological differences. In this regard, 3D cellular models can be presented as a step forward in biomedical research, allowing for mimicking tissue complexity more accurately than traditional 2D models, while also contributing to reducing the use of animal models. In cancer research, 3D models have the potential to replicate the tumor microenvironment, which is a key modulator of cancer cell behavior and drug response. These features make cancer 3D models prime tools for the preclinical study of anti-tumoral drugs, especially considering that there is still a need to develop effective anti-cancer drugs with high selectivity, minimal toxicity, and reduced side effects. Metallodrugs, especially transition-metal-based complexes, have been extensively studied for their therapeutic potential in cancer therapy due to their distinctive properties; however, despite the benefits of 3D models, their application in metallodrug testing is currently limited. Thus, this article reviews some of the most common types of 3D models in cancer research, as well as the application of 3D models in metallodrug preclinical studies.
Topics: Animals; Neoplasms; Antineoplastic Agents; Tumor Microenvironment; Models, Animal; Drug Development
PubMed: 37569291
DOI: 10.3390/ijms241511915 -
Molecules (Basel, Switzerland) Jul 2023Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or... (Review)
Review
Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to the need to continually screen natural products for effective and alternative anticancer bioactive principles. Alkaloids are chemical molecules that, due to their structural diversity, constitute a reserve for the discovery of lead compounds with interesting pharmacological activities. Several in vitro studies and a few in vivo findings have documented various cytotoxic and antiproliferative properties of alkaloids. This review describes chaetocochin J, neopapillarine, coclaurine, reflexin A, 3,10-dibromofascaplysin and neferine, which belong to different alkaloid classes with antineoplastic properties and have been identified recently from plants. Despite their low solubility and bioavailability, plant-derived alkaloids have viable prospects as sources of viable lead antitumor agents. This potential can be achieved if more research on these chemical compounds is directed toward investigating ways of improving their delivery in an active form close to target cells, preferably with no effect on neighboring normal tissues.
Topics: Humans; Alkaloids; Antineoplastic Agents; Neoplasms; Plant Extracts
PubMed: 37513450
DOI: 10.3390/molecules28145578 -
Military Medical Research Dec 2023
Topics: Humans; Ferroptosis; Melanoma; Antineoplastic Agents; Immunotherapy; Hydroxysteroid Dehydrogenases
PubMed: 38049916
DOI: 10.1186/s40779-023-00497-1 -
Molecules (Basel, Switzerland) Sep 2023Increasing cases of cancer have been a primary concern in recent decades. Developing new chemotherapeutics is challenging and has been faced with limitations, such as... (Review)
Review
Increasing cases of cancer have been a primary concern in recent decades. Developing new chemotherapeutics is challenging and has been faced with limitations, such as multidrug resistance, poor specificity, selectivity, and toxicity. The aforementioned factors contribute to treatment failure. Hybrid compounds have features that can overcome the limitations mentioned above. Chlorambucil, an anticancer drug that is used to treat prostate and breast cancer, suffers from poor aqueous solubility and specificity, a short half-life, and severe side effects, including anaemia and bone marrow suppression. It compromises the immune system, resulting in treatment failure. Hence, its combination with other pharmacophores has been reported to result in effective anticancer agents with fewer side effects and high therapeutic outcomes. Furthermore, this review gives an update (2010 to date) on the developments of chlorambucil hybrid compounds with anticancer activity, and the structure-activity relationship (SAR), and also highlights future strategies for developing novel anticancer agents.
Topics: Male; Humans; Chlorambucil; Antineoplastic Agents; Structure-Activity Relationship; Breast Neoplasms; Pharmacophore
PubMed: 37836732
DOI: 10.3390/molecules28196889 -
Biochemical Pharmacology Jul 2023Cancer therapies have several clinical challenges associated with them, namely treatment toxicity, treatment resistance and relapse. Due to factors ranging from patient... (Review)
Review
Cancer therapies have several clinical challenges associated with them, namely treatment toxicity, treatment resistance and relapse. Due to factors ranging from patient profiles to the tumour microenvironment (TME), there are several hurdles to overcome in developing effective treatments that have low toxicity that can mitigate emergence of resistance and occurrence of relapse. De novo cancer development has the highest drug attrition rates with only 1 in 10,000 preclinical candidates reaching the market. To alleviate this high attrition rate, more mimetic and sustainable preclinical models that can capture the disease biology as in the patient, are required. Organoids and next generation 3D tissue engineering is an emerging area that aims to address this problem. Advancement of three-dimensional (3D) in vitro cultures into complex organoid models incorporating multiple cell types alongside acellular aspects of tissue microenvironments can provide a system for therapeutic testing. Development of microfluidic technologies have furthermore increased the biomimetic nature of these models. Additionally, 3D bio-printing facilitates generation of tractable ex vivo models in a controlled, scalable and reproducible manner. In this review we highlight some of the traditional preclinical models used in cancer drug testing and debate how next generation organoids are being used to replace not only animal models, but also some of the more elementary in vitro approaches, such as cell lines. Examples of applications of the various models will be appraised alongside the future challenges that still need to be overcome.
Topics: Animals; Organoids; Tissue Engineering; Neoplasms; Antineoplastic Agents; Tumor Microenvironment
PubMed: 37164297
DOI: 10.1016/j.bcp.2023.115586