scholarly journals 7-epi-Clusianone, a Multi-Targeting Natural Product with Potential Chemotherapeutic, Immune-Modulating, and Anti-Angiogenic Properties

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4415 ◽  
Author(s):  
Wesley F. Taylor ◽  
Maria Yanez ◽  
Sara E. Moghadam ◽  
Mahdi Moridi Farimani ◽  
Sara Soroury ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Targeted Therapies ◽  
Acquired Resistance ◽  
Cell Types ◽  
Treatment Modalities ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Anticancer Properties ◽  
Immune Therapies ◽  
Cancer Types

Targeted therapies have changed the treatment of cancer, giving new hope to many patients in recent years. The shortcomings of targeted therapies including acquired resistance, limited susceptible patients, high cost, and high toxicities, have led to the necessity of combining these therapies with other targeted or chemotherapeutic treatments. Natural products are uniquely capable of synergizing with targeted and non-targeted anticancer regimens due to their ability to affect multiple cellular pathways simultaneously. Compounds which provide an additive effect to the often combined immune therapies and cytotoxic chemotherapies, are exceedingly rare. These compounds would however provide a strengthening bridge between the two treatment modalities, increasing their effectiveness and improving patient prognoses. In this study, 7-epi-clusianone was investigated for its anticancer properties. While previous studies have suggested clusianone and its conformational isomers, including 7-epi-clusianone, are chemotherapeutic, few cancer types have been demonstrated to exhibit sensitivity to these compounds and little is known about the mechanism. In this study, 7-epi-clusianone was shown to inhibit the growth of 60 cancer cell types and induce significant cell death in 25 cancer cell lines, while simultaneously modulating the immune system, inhibiting angiogenesis, and inhibiting cancer cell invasion, making it a promising lead compound for cancer drug discovery.

scholarly journals ANTICANCER POTENTIAL OF α-MANGOSTIN

2017 ◽  
Vol 10 (12) ◽  
pp. 440 ◽  
Author(s):  
Muchtaridi Muchtaridi ◽  
Cindy Aprillianie Wijaya
Keyword(s):  
Chemical Compounds ◽  
Cancer Drug ◽  
Garcinia Mangostana ◽  
Pharmacological Activities ◽  
Tropical Fruit ◽  
Cancer Drug Discovery ◽  
Anticancer Properties ◽  
Xanthone Derivatives ◽  
East Region ◽  
Apoptotic Activity

Objective: Mangosteen (Garcinia mangostana Linn.) is a tropical fruit originated from South East region. Mangosteen exhibiting a variety of pharmacological activities and is often used for traditional medicine. There are numerous chemical compounds contained in the pericarp of the mangosteen fruit. One of them is xanthone derivative which in some studies shows antioxidant and anticancer activity by preventing free radical and damaging cells. One of the xanthone derivatives that have the strongest anticancer properties is α-mangostin.Methods: Anticancer potential of α-mangostin was reviewed from available literature.Results: The α-mangostin shows anti-proliferative and apoptotic activity by suppressing the formation of carcinogenic compounds in various cancer cells. This review will summarize the anticancer properties of α-mangostin that may be exploited for effective cancer prevention.Conclusion: Development of α-mangostin as a chemopreventive compound can provide new opportunities for effective cancer drug discovery. α-mangostin is useful as a complementary or alternative medicine and a chemopreventive tool against cancer.

scholarly journals Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2436 ◽  
Author(s):  
Petra Grbčić ◽  
Mirela Sedić
Keyword(s):  
Colon Cancer ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Treatment Modalities ◽  
Rational Approach ◽  
Cancer Drug ◽  
Comprehensive Overview ◽  
Chemotherapy Drugs ◽  
Sphingosine 1 Phosphate

Colorectal carcinoma (CRC) is the leading cause of cancer-related deaths worldwide. Despite advances in prevention and treatment modalities for CRC, rapidly developing resistance to chemotherapy limits its effectiveness. For that reason, it is important to better understand the mechanisms that undergird the process of chemoresistance to enable design of novel anticancer agents specifically targeting malignant properties of cancer cells. Over recent decades, bioactive sphingolipid species have come under the spotlight for their recognized role in cancer development and progression, and the evidence has surfaced to support their role as regulators of anti-cancer drug resistance. Colon cancer is characterized by a shift in sphingolipid balance that favors the production and accumulation of oncogenic species such as sphingosine 1-phosphate (S1P). S1P is known to govern the processes that facilitate cancer cell growth and progression including proliferation, survival, migration, invasion and inflammation. In this review paper, we will give a comprehensive overview of current literature findings on the molecular mechanisms by which S1P turnover, transport and signaling via receptor-dependent and independent pathways shape colon cancer cell behavior and influence treatment outcome in colon cancer. Combining available modulators of S1P metabolism and signaling with standard chemotherapy drugs could provide a rational approach to achieve enhanced therapeutic response, diminish chemoresistance development and improve the survival outcome in CRC patients.

scholarly journals Cancer-Associated Fibroblasts Differentiated by Exosomes Isolated from Cancer Cells Promote Cancer Cell Invasion

2020 ◽  
Vol 21 (21) ◽  
pp. 8153
Author(s):  
Kimin Kim ◽  
Yeh Joo Sohn ◽  
Ruri Lee ◽  
Hye Ju Yoo ◽  
Ji Yoon Kang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cell Types ◽  
Cancer Drug ◽  
Cancer Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Cancer Cell Invasion

Cancer-associated fibroblasts (CAFs) in the cancer microenvironment play an essential role in metastasis. Differentiation of endothelial cells into CAFs is induced by cancer cell-derived exosomes secreted from cancer cells that transfer molecular signals to surrounding cells. Differentiated CAFs facilitate migration of cancer cells to different regions through promoting extracellular matrix (ECM) modifications. However, in vitro models in which endothelial cells exposed to cancer cell-derived exosomes secreted from various cancer cell types differentiate into CAFs or a microenvironmentally controlled model for investigating cancer cell invasion by CAFs have not yet been studied. In this study, we propose a three-dimensional in vitro cancer cell invasion model for real-time monitoring of the process of forming a cancer invasion site through CAFs induced by exosomes isolated from three types of cancer cell lines. The invasiveness of cancer cells with CAFs induced by cancer cell-derived exosomes (eCAFs) was significantly higher than that of CAFs induced by cancer cells (cCAFs) through physiological and genetic manner. In addition, different genetic tendencies of the invasion process were observed in the process of invading cancer cells according to CAFs. Our 3D microfluidic platform helps to identify specific interactions among multiple factors within the cancer microenvironment and provides a model for cancer drug development.

scholarly journals Design, Synthesis, and In Vitro Antiproliferative Activity of Hydantoin and Purine Derivatives with the 4-Acetylphenylpiperazinylalkyl Moiety

Materials ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4156
Author(s):  
Agnieszka Zagórska ◽  
Anna Czopek ◽  
Anna Jaromin ◽  
Magdalena Mielczarek-Puta ◽  
Marta Struga ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Chemical Diversity ◽  
Cancer Drug ◽  
Purine Derivatives ◽  
Design Synthesis ◽  
Cancer Drug Discovery

Cancer represents one of the most serious health problems and the second leading cause of death around the world. Heterocycles, due to their prevalence in nature as well as their structural and chemical diversity, play an immensely important role in anti-cancer drug discovery. In this paper, a series of hydantoin and purine derivatives containing a 4-acetylphenylpiperazinylalkyl moiety were designed, synthesized, and biologically evaluated for their anticancer activity on selected cancer cell lines (PC3, SW480, SW620). Compound 4, a derivative of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione, was the most effective against SW480, SW620, and PC3 cancer cell lines. Moreover, 4 has high tumor-targeting selectivity. Based on docking studies, it was concluded that R isomers of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione could be further studied as promising scaffolds for the development of thymidine phosphorylase inhibitors.

scholarly journals Identification of Potential Chemical Substrates as Fuel for Hypoxic Tumors That May Be Linked to Invadopodium Formation in Hypoxia-Induced MDA-MB-231 Breast-Cancer Cell Line

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3876
Author(s):  
Hamad Ali Hamad ◽  
Hamid Hammad Enezei ◽  
Anmar Alrawas ◽  
Noraina Muhamad Zakuan ◽  
Nurul Akmaryanti Abdullah ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Hypoxia Inducible Factor ◽  
Cancer Cell Line ◽  
Nutrient Utilization ◽  
Cancer Drug ◽  
Phenotype Microarray ◽  
Nucleotide Exchange ◽  
Cancer Drug Discovery ◽  
Nucleotide Exchange Factor ◽  
Invadopodia Formation

Hypoxia plays a significant role in solid tumors by the increased expression of hypoxia-inducible factor-1α (HIF-1α), which is known to promote cancer invasion and metastasis. Cancer-cell invasion dynamically begins with the degradation of the extracellular matrix (ECM) via invadopodia formation. The chemical substrates that are utilized by hypoxic cells as fuel to drive invadopodia formation are still not fully understood. Therefore, the aim of the study was to maintain MDA-MB-231 cells under hypoxia conditions to allow cells to form a large number of invadopodia as a model, followed by identifying their nutrient utilization. The results of the study revealed an increase in the number of cells forming invadopodia under hypoxia conditions. Moreover, Western blot analysis confirmed that essential proteins for hypoxia and invadopodia, including HIF-1α, vascular endothelial growth factor (VEGF), metallopeptidase-2 (MMP-2), and Rho guanine nucleotide exchange factor 7 (β-PIX), significantly increased under hypoxia. Interestingly, phenotype microarray showed that only 11 chemical substrates from 367 types of substrates were significantly metabolized in hypoxia compared to in normoxia. This is thought to be fuel for hypoxia to drive the invasion process. In conclusion, we found 11 chemical substrates that could have potential energy sources for hypoxia-induced invadopodia formation of these cells. This may in part be a target in the hypoxic tumor and invadopodia formation. Additionally, these findings can be used as potential carrier targets in cancer-drug discovery, such as the usage of dextrin.

scholarly journals Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1469 ◽  
Author(s):  
Kevin Zhai ◽  
Aranka Brockmüller ◽  
Peter Kubatka ◽  
Mehdi Shakibaei ◽  
Dietrich Büsselberg
Keyword(s):  
Curcuma Longa ◽  
Cell Types ◽  
Cancer Drug ◽  
Protein Aggregate ◽  
Beneficial Effects ◽  
Anticancer Properties ◽  
Natural Substances ◽  
Cancer Drug Resistance ◽  
Preclinical Trials

Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine–threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin’s low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.

Artificial intelligence in fighting cancer: A short review and trends

2017 ◽  
Vol 2 (2) ◽  
pp. 42
Author(s):  
Jovan David Rebolledo-Mendez
Keyword(s):  
Artificial Intelligence ◽  
Cancer Detection ◽  
Network Architecture ◽  
Short Review ◽  
Cancer Drug ◽  
Neural Network Architecture ◽  
Cancer Drug Discovery ◽  
Current Trends ◽  
Cancer Types ◽  
Personalized Cancer

<p>The current trends of artificial intelligence (AI) and machine learning, specifically the amazing success achieved by artificial refurbished neural network architecture deep learning (DL), algorithms used like in alpha go, could greatly benefit cancer detection, personalized cancer treatment, and cancer drug discovery. New models like DL have recently arrived and are offering a leap step into classifying cancer types and even potential drug discoveries. These targeted AI will continue emerging and will build up toward the final fight of cancer: When AI, with the help of advance sensors that will provide data, can diagnosis cancer in stage zero.</p>

scholarly journals Systematic Assessment of Tumor Purity and Its Clinical Implications

2020 ◽  
pp. 995-1005
Author(s):  
Syed Haider ◽  
Svitlana Tyekucheva ◽  
Davide Prandi ◽  
Natalie S. Fox ◽  
Jaeil Ahn ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Estimation Method ◽  
Cell Types ◽  
Cell Fraction ◽  
Estimation Methods ◽  
Tumor Purity ◽  
Genomic Analyses ◽  
Cancer Types ◽  
Molecular Profiles ◽  
Cancer Cell Fraction

PURPOSE The tumor microenvironment is complex, comprising heterogeneous cellular populations. As molecular profiles are frequently generated using bulk tissue sections, they represent an admixture of multiple cell types (including immune, stromal, and cancer cells) interacting with each other. Therefore, these molecular profiles are confounded by signals emanating from many cell types. Accurate assessment of residual cancer cell fraction is crucial for parameterization and interpretation of genomic analyses, as well as for accurately interpreting the clinical properties of the tumor. MATERIALS AND METHODS To benchmark cancer cell fraction estimation methods, 10 estimators were applied to a clinical cohort of 333 patients with prostate cancer. These methods include gold-standard multiobserver pathology estimates, as well as estimates inferred from genome, epigenome, and transcriptome data. In addition, two methods based on genomic and transcriptomic profiles were used to quantify tumor purity in 4,497 tumors across 12 cancer types. Bulk mRNA and microRNA profiles were subject to in silico deconvolution to estimate cancer cell–specific mRNA and microRNA profiles. RESULTS We present a systematic comparison of 10 tumor purity estimation methods on a cohort of 333 prostate tumors. We quantify variation among purity estimation methods and demonstrate how this influences interpretation of clinico-genomic analyses. Our data show poor concordance between pathologic and molecular purity estimates, necessitating caution when interpreting molecular results. Limited concordance between DNA- and mRNA-derived purity estimates remained a general pan-cancer phenomenon when tested in an additional 4,497 tumors spanning 12 cancer types. CONCLUSION The choice of tumor purity estimation method may have a profound impact on the interpretation of genomic assays. Taken together, these data highlight the need for improved assessment of tumor purity and quantitation of its influences on the molecular hallmarks of cancers.

scholarly journals A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology

2020 ◽  
Author(s):  
Xiaoxi Xu ◽  
Shuzhong Wang ◽  
jun zhou ◽  
Jing Chen ◽  
yujun Huang ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Immune Cell ◽  
Tumor Xenograft ◽  
Cancer Drug ◽  
Matched Pairs ◽  
Cancer Drug Discovery ◽  
Cancer Pharmacology ◽  
Immune Therapies

Abstract Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including in population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting “biological equivalence or interchangeability” between the two. Here we demonstrate the applications of PDXO biobank for HTS “matrix” screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.

scholarly journals Effects of Bioactive Marine-Derived Liposomes on Two Human Breast Cancer Cell Lines

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 211 ◽  
Author(s):  
Jie Li ◽  
Kamil Elkhoury ◽  
Claire Barbieux ◽  
Michel Linder ◽  
Stéphanie Grandemange ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Cancer Cell ◽  
Cell Types ◽  
Breast Cancer Cell Lines ◽  
Anticancer Properties ◽  
Anticancer Effects ◽  
Delivery Strategies ◽  
Mcf 7

Breast cancer is the leading cause of death from cancer among women. Higher consumption of dietary marine n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) is associated with a lower risk of breast cancer. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are two n-3 LC-PUFAs found in fish and exert anticancer effects. In this study, natural marine-derived lecithin that is rich in various polyunsaturated fatty acids (PUFAs) was extracted from salmon heads and transformed into nanoliposomes. These nanoliposomes were characterized and cultured with two breast cancer lines (MCF-7 and MDA-MB-231). The nanoliposomes decreased the proliferation and the stiffness of both cancer cell types. These results suggest that marine-derived lecithin possesses anticancer properties, which may have an impact on developing new liposomal delivery strategies for breast cancer treatment.

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