scholarly journals Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhaowu Ma ◽  
Clariis Yi-Ning Woon ◽  
Chen-Guang Liu ◽  
Jun-Ting Cheng ◽  
Mingliang You ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Drug Repurposing ◽  
Potential Candidate ◽  
Anticancer Activities ◽  
Cellular Mechanisms ◽  
Lead Compounds ◽  
Pharmacokinetic Properties ◽  
Proliferation And Metastasis

Cancer has become a global health problem, accounting for one out of six deaths. Despite the recent advances in cancer therapy, there is still an ever-growing need for readily accessible new therapies. The process of drug discovery and development is arduous and takes many years, and while it is ongoing, the time for the current lead compounds to reach clinical trial phase is very long. Drug repurposing has recently gained significant attention as it expedites the process of discovering new entities for anticancer therapy. One such potential candidate is the antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo. In this review, major molecular and cellular mechanisms underlying the anticancer effect of artemisinin and its derivatives are summarised. Furthermore, major mechanisms of action and some key signaling pathways of this group of compounds have been reviewed to explore potential targets that contribute to the proliferation and metastasis of tumor cells. Despite its established profile in malaria treatment, pharmacokinetic properties, anticancer potency, and current formulations that hinder the clinical translation of artemisinin as an anticancer agent, have been discussed. Finally, potential solutions or new strategies are identified to overcome the bottlenecks in repurposing artemisinin-type compounds as anticancer drugs.

scholarly journals An Update on the Anticancer Activity of Xanthone Derivatives: A Review

2021 ◽  
Vol 14 (11) ◽  
pp. 1144
Author(s):  
Yehezkiel Steven Kurniawan ◽  
Krisfian Tata Aneka Priyangga ◽  
Jumina ◽  
Harno Dwi Pranowo ◽  
Eti Nurwening Sholikhah ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Rna Binding ◽  
Annual Number ◽  
Synthesis Methods ◽  
Anticancer Activities ◽  
Xanthone Derivatives ◽  
Almost All

The annual number of cancer deaths continues increasing every day; thus, it is urgent to search for and find active, selective, and efficient anticancer drugs as soon as possible. Among the available anticancer drugs, almost all of them contain heterocyclic moiety in their chemical structure. Xanthone is a heterocyclic compound with a dibenzo-γ-pyrone framework and well-known to have “privileged structures” for anticancer activities against several cancer cell lines. The wide anticancer activity of xanthones is produced by caspase activation, RNA binding, DNA cross-linking, as well as P-gp, kinase, aromatase, and topoisomerase inhibition. This anticancer activity depends on the type, number, and position of the attached functional groups in the xanthone skeleton. This review discusses the recent advances in the anticancer activity of xanthone derivatives, both from natural products isolation and synthesis methods, as the anticancer agent through in vitro, in vivo, and clinical assays.

scholarly journals Anticancer Effects and Mechanisms of OSW-1 Isolated From Ornithogalum saundersiae: A Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhixin Zhan ◽  
Ziqiang Liu ◽  
Jiacheng Lai ◽  
Chaochao Zhang ◽  
Yong Chen ◽  
...  
Keyword(s):  
Premature Death ◽  
Potential Candidate ◽  
Rapid Population Growth ◽  
Anticancer Activities ◽  
Dark Cloud ◽  
Anticancer Effects ◽  
Incidence And Mortality ◽  
Growth And Aging

For centuries, cancer has been a lingering dark cloud floating on people’s heads. With rapid population growth and aging worldwide, cancer incidence and mortality are growing rapidly. Despite major advances in oncotherapy including surgery, radiation and chemical therapy, as well as immunotherapy and targeted therapy, cancer is expected be the leading cause of premature death in this century. Nowadays, natural compounds with potential anticancer effects have become an indispensable natural treasure for discovering clinically useful agents and made remarkable achievements in cancer chemotherapy. In this regards, OSW-1, which was isolated from the bulbs of Ornithogalum saundersiae in 1992, has exhibited powerful anticancer activities in various cancers. However, after almost three decades, OSW-1 is still far from becoming a real anticancer agent for its anticancer mechanisms remain unclear. Therefore, in this review we summarize the available evidence on the anticancer effects and mechanisms of OSW-1 in vitro and in vivo, and some insights for researchers who are interested in OSW-1 as a potential anticancer drug. We conclude that OSW-1 is a potential candidate for anticancer drugs and deserves further study.

scholarly journals Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

Toxics ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 24
Author(s):  
Fernanda Malhão ◽  
Alice Abreu Ramos ◽  
Ana Catarina Macedo ◽  
Eduardo Rocha
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Drugs ◽  
3D Culture ◽  
In Vivo Studies ◽  
Comparative Approach ◽  
Anticancer Activities ◽  
Breast Cell Lines

Seaweed bioactive compounds have shown anticancer activities in in vitro and in vivo studies. However, tests remain limited, with conflicting results, and effects in combination with anticancer drugs are even scarcer. Here, the cytotoxic effects of five seaweed compounds (astaxanthin, fucoidan, fucosterol, laminarin, and phloroglucinol) were tested alone and in combination with anticancer drugs (cisplatin—Cis; and doxorubicin—Dox), in breast cell lines (three breast cancer (BC) subtypes and one non-tumoral). The combinations revealed situations where seaweed compounds presented potentiation or inhibition of the drugs’ cytotoxicity, without a specific pattern, varying according to the cell line, concentration used for the combination, and drug. Fucosterol was the most promising compound, since: (i) it alone had the highest cytotoxicity at low concentrations against the BC lines without affecting the non-tumoral line; and (ii) in combination (at non-cytotoxic concentration), it potentiated Dox cytotoxicity in the triple-negative BC cell line. Using a comparative approach, monolayer versus 3D cultures, further investigation assessed effects on cell viability and proliferation, morphology, and immunocytochemistry targets. The cytotoxic and antiproliferative effects in monolayer were not observed in 3D, corroborating that cells in 3D culture are more resistant to treatments, and reinforcing the use of more complex models for drug screening and a multi-approach that should include histological and ICC analysis.

scholarly journals Anti-Cancer Constituents from Plants: Mini Review

2020 ◽  
Vol 19 (1) ◽  
pp. 83-96
Author(s):  
Mohammad Kaisarul Islam ◽  
Animesh Chandra Barman ◽  
Nazmul Qais
Keyword(s):  
Treatment Options ◽  
Minor Effect ◽  
Synthetic Approach ◽  
Anticancer Activities ◽  
Anticancer Properties ◽  
Lead Compounds ◽  
Cellular Factors ◽  
Anti Cancer

Now-a-days, cancer is a major concern globally, for which a large number of deaths occur annually, instead of the accessibility to various treatment options. Nevertheless, the latest treatment options are principally conglomerate with many side effects. Consequently, the development of an effective and competent anticancer therapy with the lower or minimum adverse or unwanted minor effect is the prime direction of research in the fields of natural product chemistry, drug design, and drug discovery. Phytochemicals available in plants have already been proven as prospective candidates in this regard. In general, phytochemicals are non-selective in their functions and restricted due to their differential activity on cancer cells along with the normal cells. As a consequence, researchers show their interest in isolating bioactive phytochemicals from nature with potent anticancer properties and generate lead compounds based on the natural skeleton of a molecule as a synthetic approach. Several phytomolecules have already been in existence for their in-vitro and in-vivo anticancer activities. This article deals with these lead phytomolecules from fifty-two species belong to thirty-five families with their reported mechanisms of action on nuclear and cellular factors involved in the treatment of carcinogenesis. Dhaka Univ. J. Pharm. Sci. 19(1): 83-96, 2020 (June)

scholarly journals Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 360 ◽  
Author(s):  
Vivek Kaushik ◽  
Juan Yakisich ◽  
Anil Kumar ◽  
Neelam Azad ◽  
Anand Iyer
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Targeted Drug Delivery ◽  
Ion Homeostasis ◽  
Anticancer Activities ◽  
In Vivo Models ◽  
Potential Use

Ion homeostasis is extremely important for the survival of both normal as well as neoplastic cells. The altered ion homeostasis found in cancer cells prompted the investigation of several ionophores as potential anticancer agents. Few ionophores, such as Salinomycin, Nigericin and Obatoclax, have demonstrated potent anticancer activities against cancer stem-like cells that are considered highly resistant to chemotherapy and responsible for tumor relapse. The preclinical success of these compounds in in vitro and in vivo models have not been translated into clinical trials. At present, phase I/II clinical trials demonstrated limited benefit of Obatoclax alone or in combination with other anticancer drugs. However, future development in targeted drug delivery may be useful to improve the efficacy of these compounds. Alternatively, these compounds may be used as leading molecules for the development of less toxic derivatives.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances

2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin
Keyword(s):  
Drug Discovery ◽  
Chagas Disease ◽  
Drug Candidates ◽  
Lead Compounds ◽  
New Drug ◽  
Compound Libraries ◽  
Screening Assays ◽  
Cruzi Infection

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.

scholarly journals EphA2 super-enhancer promotes tumor progression by recruiting FOSL2 and TCF7L2 to activate the target gene EphA2

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Shuang Cui ◽  
Qiong Wu ◽  
Ming Liu ◽  
Mu Su ◽  
ShiYou Liu ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Target Gene ◽  
Super Enhancer ◽  
Proliferation And Metastasis ◽  
Active Transcription ◽  
Hct 116 ◽  
Large Clusters

AbstractSuper-enhancers or stretch enhancers (SEs) consist of large clusters of active transcription enhancers which promote the expression of critical genes that define cell identity during development and disease. However, the role of many super-enhancers in tumor cells remains unclear. This study aims to explore the function and mechanism of a new super-enhancer in various tumor cells. A new super-enhancer that exists in a variety of tumors named EphA2-Super-enhancer (EphA2-SE) was found using multiple databases and further identified. CRISPR/Cas9-mediated deletion of EphA2-SE results in the significant downregulation of its target gene EphA2. Mechanistically, we revealed that the core active region of EphA2-SE comprises E1 component enhancer, which recruits TCF7L2 and FOSL2 transcription factors to drive the expression of EphA2, induce cell proliferation and metastasis. Bioinformatics analysis of RNA-seq data and functional experiments in vitro illustrated that EphA2-SE deletion inhibited cell growth and metastasis by blocking PI3K/AKT and Wnt/β-catenin pathway in HeLa, HCT-116 and MCF-7 cells. Overexpression of EphA2 in EphA2-SE−/− clones rescued the effect of EphA2-SE deletion on proliferation and metastasis. Subsequent xenograft animal model revealed that EphA2-SE deletion suppressed tumor proliferation and survival in vivo. Taken together, these findings demonstrate that EphA2-SE plays an oncogenic role and promotes tumor progression in various tumors by recruiting FOSL2 and TCF7L2 to drive the expression of oncogene EphA2.

scholarly journals Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 498
Author(s):  
Mariaevelina Alfieri ◽  
Antonietta Leone ◽  
Alfredo Ambrosone
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Plant Biotechnology ◽  
Bioactive Metabolites ◽  
Anticancer Activities ◽  
Long Distance ◽  
In Vivo Models ◽  
Therapeutic Tools

Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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