Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms

2020 ◽  
Vol 20 (8) ◽  
pp. 918-931
Author(s):  
Milad Ashrafizadeh ◽  
Reza Mohammadinejad ◽  
Saeed Samarghandian ◽  
Habib Yaribeygi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Side Effects ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Malignant Cell ◽  
Malignant Cells ◽  
High Potency ◽  
Cancer Management ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Proliferation And Metastasis

Cancer management and/or treatment require a comprehensive understanding of the molecular and signaling pathways involved. Recently, much attention has been directed to these molecular and signaling pathways, and it has been suggested that a number of biomolecules/players involved in such pathways, such as PI3K/Akt, NF-κB, STAT, and Nrf2 contribute to the progression, invasion, proliferation, and metastasis of malignant cells. Synthetic anti-tumor agents and chemotherapeutic drugs have been a mainstay in cancer therapy and are widely used to suppress the progression and, hopefully, halt the proliferation of malignant cells. However, these agents have some undesirable side-effects and, therefore, naturally-occurring compounds with high potency and fewer side-effects are now of great interest. Osthole is a plant-derived chemical compound that can inhibit the proliferation of malignant cells and provide potent anti-cancer effects in various tissues. Therefore, in this review, we presented the main findings concerning the potential anti-tumor effects of osthole and its derivatives and described possible molecular mechanisms by which osthole may suppress malignant cell proliferation in different tissues.

scholarly journals Caspase-Independent Regulated Necrosis Pathways as Potential Targets in Cancer Management

2021 ◽  
Vol 10 ◽  
Author(s):  
Jianyao Lou ◽  
Yunxiang Zhou ◽  
Zengyu Feng ◽  
Mindi Ma ◽  
Yihan Yao ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Multiple Modes ◽  
Cancer Management ◽  
Regulated Necrosis ◽  
Anti Cancer ◽  
Cancer Initiation

Regulated necrosis is an emerging type of cell death independent of caspase. Recently, with increasing findings of regulated necrosis in the field of biochemistry and genetics, the underlying molecular mechanisms and signaling pathways of regulated necrosis are gradually understood. Nowadays, there are several modes of regulated necrosis that are tightly related to cancer initiation and development, including necroptosis, ferroptosis, parthanatos, pyroptosis, and so on. What’s more, accumulating evidence shows that various compounds can exhibit the anti-cancer effect via inducing regulated necrosis in cancer cells, which indicates that caspase-independent regulated necrosis pathways are potential targets in cancer management. In this review, we expand the molecular mechanisms as well as signaling pathways of multiple modes of regulated necrosis. We also elaborate on the roles they play in tumorigenesis and discuss how each of the regulated necrosis pathways could be therapeutically targeted.

scholarly journals Vitamin E beyond Its Antioxidant Label

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 634
Author(s):  
Anca Ungurianu ◽  
Anca Zanfirescu ◽  
Georgiana Nițulescu ◽  
Denisa Margină
Keyword(s):  
Vitamin E ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protective Effects ◽  
Cellular Effects ◽  
Inflammatory Status ◽  
Anti Cancer ◽  
Key Factor ◽  
Exciting Potential ◽  
Underlying Mechanisms

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

scholarly journals ACNPD: The Database for Elucidating the Relationships Between Natural Products, Compounds, Molecular Mechanisms, and Cancer Types

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojie Tan ◽  
Jiahui Fu ◽  
Zhaoxin Yuan ◽  
Lingjuan Zhu ◽  
Leilei Fu
Keyword(s):  
Natural Products ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cancer Drugs ◽  
Internal Factors ◽  
Online Resource ◽  
Anti Cancer ◽  
Cancer Types

Objectives: Cancer is well-known as a collection of diseases of uncontrolled proliferation of cells caused by mutated genes which are generated by external or internal factors. As the mechanisms of cancer have been constantly revealed, including cell cycle, proliferation, apoptosis and so on, a series of new emerging anti-cancer drugs acting on each stage have also been developed. It is worth noting that natural products are one of the important sources for the development of anti-cancer drugs. To the best of our knowledge, there is not any database summarizing the relationships between natural products, compounds, molecular mechanisms, and cancer types.Materials and methods: Based upon published literatures and other sources, we have constructed an anti-cancer natural product database (ACNPD) (http://www.acnpd-fu.com/). The database currently contains 521 compounds, which specifically refer to natural compounds derived from traditional Chinese medicine plants (derivatives are not considered herein). And, it includes 1,593 molecular mechanisms/signaling pathways, covering 10 common cancer types, such as breast cancer, lung cancer and cervical cancer.Results: Integrating existing data sources, we have obtained a large amount of information on natural anti-cancer products, including herbal sources, regulatory targets and signaling pathways. ACNPD is a valuable online resource that illustrates the complex pharmacological relationship between natural products and human cancers.Conclusion: In summary, ACNPD is crucial for better understanding of the relationships between traditional Chinese medicine (TCM) and cancer, which is not only conducive to expand the influence of TCM, but help to find more new anti-cancer drugs in the future.

scholarly journals Matrine inhibits the development and progression of ovarian cancer by repressing cancer associated phosphorylation signaling pathways

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xi Zhang ◽  
Guoqing Hou ◽  
Andong Liu ◽  
Hui Xu ◽  
Yang Guan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Ovarian Cancer Cells

Abstract Ovarian cancer remains the most lethal gynecologic malignancy with late detection and acquired chemoresistance. Advanced understanding of the pathophysiology and novel treatment strategies are urgently required. A growing body of proteomic investigations suggest that phosphorylation has a pivotal role in the regulation of ovarian cancer associated signaling pathways. Matrine has been extensively studied for its potent anti-tumor activities. However, its effect on ovarian cancer cells and underlying molecular mechanisms remain unclear. Herein we showed that matrine treatment inhibited the development and progression of ovarian cancer cells by regulating proliferation, apoptosis, autophagy, invasion and angiogenesis. Matrine treatment retarded the cancer associated signaling transduction by decreasing the phosphorylation levels of ERK1/2, MEK1/2, PI3K, Akt, mTOR, FAK, RhoA, VEGFR2, and Tie2 in vitro and in vivo. Moreover, matrine showed excellent antitumor effect on chemoresistant ovarian cancer cells. No obvious toxic side effects were observed in matrine-administrated mice. As the natural agent, matrine has the potential to be the targeting drug against ovarian cancer cells with the advantages of overcoming the chemotherapy resistance and decreasing the toxic side effects.

Molecular Mechanisms Underlying Cancer Preventive and Therapeutic Potential of Algal Polysaccharides

2019 ◽  
Vol 25 (11) ◽  
pp. 1210-1235 ◽  
Author(s):  
Soraya Sajadimajd ◽  
Saeideh Momtaz ◽  
Pouya Haratipour ◽  
Fardous F. El-Senduny ◽  
Amin Iran Panah ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Anticancer Agents ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Sulfated Polysaccharides ◽  
Cochrane Library ◽  
Therapeutic Effects ◽  
Cancer Management ◽  
Algal Polysaccharides

Background: Algal polysaccharide and oligosaccharide derivatives have been shown to possess a variety of therapeutic potentials and drug delivery applications. Algal polysaccharides contain sulfated sugar monomers derived from seaweed including brown, red, and green microalgae. Here, in this review, the recent progress of algal polysaccharides’ therapeutic applications as anticancer agents, as well as underlying cellular and molecular mechanisms was investigated. Moreover, recent progress in the structural chemistry of important polysaccharides with anticancer activities were illustrated. Methods: Electronic databases including “Scopus”, “PubMed”, and “Cochrane library” were searched using the keywords “cancer”, or “tumor”, or “malignancy” in title/abstract, along with “algae”, or “algal” in the whole text until July 2018. Only English language papers were included. Results: The most common polysaccharides involved in cancer management were sulfated polysaccharides, Fucoidans, Carageenans, and Ulvan from different species of algae that have been recognized in vitro and in vivo. The underlying anticancer mechanisms of algal polysaccharides included induction of apoptosis, cell cycle arrest, modulation of transduction signaling pathways, suppression of migration and angiogenesis, as well as activation of immune responses and antioxidant system. VEGF/VEGFR2, TGFR/Smad/Snail, TLR4/ROS/ER, CXCL12/ CXCR4, TGFR/Smad7/Smurf2, PI3K/AKT/mTOR, PBK/TOPK, and β-catenin/Wnt are among the main cellular signaling pathways which have a key role in the preventive and therapeutic effects of algal polysaccharides against oncogenesis. Conclusion: Algal polysaccharides play a crucial role in the management of cancer and may be considered the next frontier in pharmaceutical research. Further well-designed clinical trials are mandatory to evaluate the efficacy and safety of algal polysaccharides in patients with cancer.

scholarly journals Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zahra Nozhat ◽  
Shabnam Heydarzadeh ◽  
Zahra Memariani ◽  
Amirhossein Ahmadi
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Side Effects ◽  
Combination Therapy ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Potential Candidate ◽  
Anti Cancer

Abstract Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

A novel nitric oxide-donor-ferulic acid hybrid inhibits proliferation and metastasis of human lung cancer A549 cells via regulation of multiple signaling pathways

2019 ◽  
Author(s):  
Shi-Jun Yue ◽  
Peng-Xuan Zhang ◽  
Yue Zhu ◽  
Nian-Guang Li ◽  
Yan-Yan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathways ◽  
Human Lung ◽  
A549 Cells ◽  
Mitogen Activated Protein Kinase ◽  
Human Lung Cancer ◽  
No Donor ◽  
Anti Cancer ◽  
Mitogen Activated Protein ◽  
Proliferation And Metastasis

Lung cancer is one of the most common malignancies as well as an increasing cause of cancer-related deaths. Nitric oxide (NO)-donor-ferulic acid (FA) hybrids, in our previous study, were designed and synthesized, which exhibited positive anti-cancer activities, especially one compound labelled as FXS-3. In this study, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed and revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells by inducing cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and suppressed the mitogen-activated protein kinase (MAPK), AKT/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by inhibiting MAPK, AKT/mTOR and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about NO-donor-FA hybrids.

Thymoquinone, an Active Compound of Nigella sativa: Role in Prevention and Treatment of Cancer

2020 ◽  
Vol 21 (11) ◽  
pp. 1028-1041 ◽  
Author(s):  
Saleh A. Almatroodi ◽  
Ahmad Almatroudi ◽  
Mohammed A. Alsahli ◽  
Amjad A. Khan ◽  
Arshad H. Rahmani
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Active Compound ◽  
Nigella Sativa ◽  
Cancer Drugs ◽  
Normal Cells ◽  
Anti Cancer ◽  
Cell Signaling Pathways

Background: Cancer is the leading cause of death worldwide and the current mode of cancer treatment causes side effects on normal cells and are still the key challenges in its’ treatment. However, natural products or active compounds of medicinal plants have shown to be safe, affordable, and effective in diseases cure. Methods: In this context, scientific studies evidence the health-promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory, and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed anti-neoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells,and inhibiting the initiation, migration, invasion, and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB, and oncogenes. Results: The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improves the efficacy of drugs which is evident by decrease resistance to drugs and regulation of various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus, TM, in combination with anti-cancer drugs, can be a good strategy in the management of various types of cancer. Conclusion: In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer-based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.

Resveratrol in the treatment of neuroblastoma: a review

2020 ◽  
Vol 31 (8) ◽  
pp. 873-881
Author(s):  
Kamil Leis ◽  
Aleksandra Baska ◽  
Weronika Bereźnicka ◽  
Agata Marjańska ◽  
Ewelina Mazur ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Cell Necrosis ◽  
Tumor Mass ◽  
P21 Protein ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Therapeutic Doses ◽  
Anti Tumor Activity

AbstractResveratrol, polyphenol naturally occurring in grapes or nuts, has anti-cancer properties in the treatment of neuroblastoma – the most common childhood solid tumor. It affects cancer cells by increasing apoptosis, inducing cell necrosis and reducing tumor mass. Mechanism of action – (1) converting procaspases, mainly procaspases three and nine into active forms – caspases, (2) blocking kinases, and also (3) leading the cell to the S-cell cycle, where it is most effective while increasing the concentration of cyclin E and lowering the concentration of p21 protein. In vitro, as well as, rodent animal models studies are available and show promising results. Therapeutic doses, currently within 10–100 μmol/L, are also being tested, as well as other forms of resveratrol, such as its trans-4,4′-dihydroxystilbene analog and polyphenol lipoconjugates. In our review, we presented the known molecular mechanisms of polyphenol anti-tumor activity against neuroblastoma and discussed the studies confirming its effectiveness.

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