The Effect of Acetylsalicylic Acid (ASA) on the Mechanical Properties of Breast Cancer Epithelial Cells

Background: In most communities, the risk of developing breast cancer is increasing. By affecting the cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes and actin filaments, acetylsalicylic acid (Aspirin) has been shown to reduce the risk of breast cancer and prevent cell migration in both laboratory and clinical studies. Methods: The purpose of this study is to determine the mechanical properties of normal and cancerous breast tissue cells, as well as the short-term effect of aspirin on cancer cells. To this end, the mechanical properties and deformation of three cell types were investigated: healthy MCF-10 breast cells, MCF-7 breast cancer cells, and MCF-7 breast cancer cells treated with a 5 µM aspirin solution. Atomic Force Microscopy (AFM) was used to determine the mechanical properties of the cells. Cell deformation was analyzed in all groups, and Young's modulus was calculated using the Hertz model. Result: According to the obtained data, cancer cells deformed at a rate half that of healthy cells. Nonetheless, when aspirin was used, cancer cells deformed similarly to healthy cells. Additionally, healthy cells' Young's modulus was calculated to be approximately three times that of cancer cells, which was placed closer to that of healthy cells by adding aspirin to Young's modulus. Conclusion: Cell strength appears to have increased due to aspirin's intervention on actin filaments and cytoskeletons, and the mechanical properties of breast cancer cells have become more similar to those of normal cells. The likelihood of cell migration and metastasis decreases as cell strength increases.

Network Pharmacology-Based Prediction and Verification of Shikonin for the mechanism treating colorectal cancer

Background: Shikonin (SKN), a naturally occurring naphthoquinone, is a major active chemical component isolated from Lithospermum erythrorhizon Sieb Zucc, Arnebia euchroma (Royle) Johnst, or Arnebia guttata Bunge, and commonly used to treat viral infection, inflammation, and cancer. However, the underlying mechanism has not been elucidated Objective: This study aims to explore the antitumor mechanism of SKN in colorectal cancer (CRC) through network pharmacology and cell experiments. Methods: Using SymMap database and Genecards to predict the potential targets of SKN and CRC, while the cotargets were obtained by Venn diagram. The cotargets were imported into website of String and DA DAVID, constructing the protein-protein interaction (PPI) network, performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the Compound-Target-Pathway (C-T-P) network was generated by connecting potential pathways with the corresponding targets. Results: According to the results of network pharmacological analysis, the cell experiments were used to verify the key signal pathway. The most relevant target of SKN for the treatment of CRC was PI3K/Akt signaling pathway. SKN inhibited CRC cells (HT29 and HCT116) proliferation, migration, and invasion, and promoted cell apoptosis by targeting IL6 and inhibiting the IL6R/PI3K/Akt signaling pathway. SKN promotes apoptosis and suppresses CRC cells (HT29 and HCT116) activity through the PI3K-Akt signaling pathway. Conclusion: This research not only provides a theoretical and experimental basis for more in-depth studies but also offers an efficient method for the rational utilization of a series of Traditional Chinese medicines as anti-CRC drugs.

β-Estradiol Induces Mitochondrial Apoptosis in Cervical Cancer Through the Suppression of AKT/NF-κB Signaling Pathway

Background: Cervical cancer is the fourth most prevalent gynecological cancer worldwide, which threatens women's health and causes cancer-related mortality. In the search for effective anticervical cancer drugs, we discovered that β-estradiol (E2), a patent drug for estrogen deficiency syndrome treatment, displays the most potent cytotoxicity against HeLa cells. Objective: This study aims to evaluate the growth inhibitory effect of β-estradiol on HeLa cells and explore its underlying mechanisms. Methods: CCK-8 assay was used to evaluate the cytotoxicity of 6 compounds against HeLa cells. Flow cytometric analysis and Hoechst 33258 staining assay were performed to detect cell cycle arrest and apoptosis induction. The collapse of the mitochondrial potential was observed by the JC-1 staining assay. The expression levels of proteins were examined by western blotting. Results: β-Estradiol, at high concentration, displays potent cytotoxicity against HeLa cells with an IC50 value of 18.71 ± 1.57 μM for 72 h treatment. β-Estradiol induces G2/M cell cycle arrest through downregulating Cyclin B1 and p-CDK1. In addition, β-estradiol-induced apoptosis is accompanied by the loss of mitochondrial potential, activation of the Caspase family, and altered Bax/Bcl-2 ratio. β-Estradiol markedly decreased the expression level of p-AKT and p-NF-κB. Conclusion: This study demonstrated that β-estradiol induces mitochondrial apoptosis in cervical cancer through the suppression of the AKT/NF-κB signaling pathway, indicating that β-estradiol may serve as a potential agent for cervical cancer treatment.

The Synthesis, Structural Modification and Mode of Anticancer Action of Evodiamine: a review

Background: Finding novel antitumor reagents from naturally occurring alkaloids is a widely accepted strategy. Evodiamine, a tryptamine indole alkaloid isolated from Evodia rutaecarpa, has a wide range of biological activities, such as antitumor, anti-inflammation, and anti-bacteria. Hence, research works on the structural modification of evodiamine will facilitate the discovery of new antitumor drugs. Objective: The recent advances in the synthesis of evodiamine, and studies on the drug design, biological activities, and structure-activity-relationships of its derivatives, published in patents and primary literatures, are reviewed in this paper. Methods: The literatures, including patents and follow-up research papers from 2015 to 2020, related to evodiamine is searched in the Scifinder, PubMed, Espacenet, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The key words are evodiamine, synthesis, modification, anticancer, mechanism. Results: The synthesis of evodiamine are summarized. Then, structural modifications of evodiamine are described, and the possible modes of actions are discussed. Conclusion: Evodiamine has a 6/5/6/6/6 ring system, and the structural modifications are focused on ring A, D, E, C5, N-13, and N-14. Some compounds show promising anticancer potentials and warrant further study.

The Impact of Polyphenolic in The Management of Breast Cancer: Mechanistic Aspects and Recent Patents

Background: Breast cancer is the most frequently diagnosed type of cancer in women (2.1 million) and stands as the fifth leading cause of death. Several treatment strategies are available such as surgical resection, radiation, hormonal therapy, and conventional chemotherapy that are associated with severe adverse effects on the patients. Objective: This review aims to summarize the different studies (in vitro, in vivo, and new patents) concerning the therapeutic potential of plant polyphenolics in the management of breast cancer published in the period from January 2016 to January 2021. Moreover, this review will focus on the underlying mechanism of action and molecular characteristics of these compounds. Methods: The data of this review were collected from different scientific databases such as PubMed, Science Direct, Google Scholarship, sci-finder, and Egyptian Knowledge bank (EKB). Results: During the last period (2016-2021), the in vitro studies investigated about 52 natural compounds of polyphenolic nature with promising anti-breast cancer, while fourteen compounds were reported via in vivo studies. Besides, there were about fifteen compounds registered as patent drugs. Different mechanisms of action and molecular targets were reported to provide a great clarified base and precise reflection for the anticancer properties of these compounds against breast cancer. Conclusion: Polyphenolics represent a plentiful sources of anticancer lead compounds that stand against the progression of breast cancer invasion and metastasis.

Anti-cancer Research on Arnebiae Radix-derived Naphthoquinone in Recent Five Years

Background: In recent years, many naphthoquinone compounds with anticancer activity have been identified in Arnebiae Radix, and some of them have the potential to be developed into anticancer drugs. Objective: This article aimed to provide a comprehensive overview of the anticancer effects of naphthoquinone compounds through a detailed review of literature and Chinese patents, and discuss their potential to be developed as anticancer drugs for clinical application. Methods: Research papers were collected through the databases of PubMed, Cnki and SciDirect using keyword searches “naphthoquinone compounds” and “anticancer”. The keywords of “shikonin” and “shikonin derivatives” were also used in PubMed, Cnki and SciDirect databases to collect research articles. The Chinese patents were collected using the Cnki patent database. Results: Naphthoquinone compounds have been found to possess anti-cancer activity, and their modes of action are associated with inducing apoptosis, inhibiting cancer cell proliferation, promoting autophagy in cancer cells, anti-cancer angiogenesis and inhibition of cell adhesion, invasion and metastasis, inhibiting glycolysis and inhibiting DNA topoisomerase activity. Conclusion: Most of the naphthoquinone compounds show effective anti-cancer activity in vitro. The structure modification of naphthoquinone aims to develop anti-cancer drugs with high efficacy and low toxicity.

Recent Progress in Natural Anticancer Agents Discovery from Tea (Camellia sinensis): A Review

Background: Tea, as the bud from the plant Camellia sinensis, is the most consumed popular beverage just next to water; especially green tea has gained much attention because of its health effects. The anticancer effects of tea components including tea polyphenols, in particular epigallocatechin gallate and tea polysaccharides, are widely investigated in recent years. Objective: Based on the articles and patents published in the last 10 years, this review focuses on the structural activities and molecular mechanisms of the anticancer effects of tea components (mainly tea polyphenols and tea polysaccharides), with a view to providing references for future anticancer studies of tea. Methods: In the database, a literature search was conducted with “tea polyphenols”, “tea polysaccharides”, “theanine” and “anticancer” as the key words, and the limited time range was “2010-2021”. After sorting out and analyzing the retrieval results, the structure, activity and molecular mechanism, as well as the research progress on the structural modification, drug delivery system and toxicology of natural agents in tea in recent years were summarized. Results: We found that the natural anticancer agents in tea mainly include tea polyphenols, tea polysaccharides, theanine, caffeine and other components by summarizing the literature. The anticancer mechanisms can be divided into the induction of cell apoptosis, inhibition of cell proliferation, metastasis and invasion, and inhibition of angiogenesis. In the past 10 years, there were few literatures on the structural modification, drug delivery system and toxicological evaluation of natural anticancer agents in tea, and there were reports of novel research on nano preparations. The studies showed that nano preparation technology could effectively improve the bioavailability and targeting treatment of tea anticancer components. In addition, in the past decade, patents on tea and natural anticancer agents in tea were relatively rich, among which pharmaceutic preparation patents were the majority, and tea polyphenols were the main ones. Conclusion: This paper concluded that there are many kinds of natural anticancer agents in tea, and the anticancer mechanism is complex. Further research on the structural modification, drug delivery system and toxicological evaluation of relevant anticancer active components can be carried out. In general, tea components as new anticancer substances have a certain potential for development. In addition, future research can be focused on the comprehensive study of the structure-activity relationship, the in-depth study of the molecular mechanism, the in-depth understanding of the anticancer effects in vivo, and the verification of large-scale production.

Non-histone methylation of SET7/9 and its biological functions

Background: (su(var)-3-9,enhancer-of-zeste,trithorax) domain-containing protein 7/9 (SET7/9) is a member of the protein lysine methyltransferases (PLMTs or PKMTs) family. It contains a SET domain. Recent studies demonstrate that SET7/9 methylates both lysine 4 of histone 3 (H3-K4) and lysine(s) of non-histone proteins, including transcription factors, tumor suppressors, and membrane-associated receptors. Objective: This article mainly reviews the non-histone methylation effects of SET7/9 and its functions in tumorigenesis and development. Methods: PubMed was screened for this information. Results: SET7/9 plays a key regulatory role in various biological processes such as cell proliferation, transcription regulation, cell cycle, protein stability, cardiac morphogenesis, and development. In addition, SET7/9 is involved in the pathogenesis of hair loss, breast cancer progression, human carotid plaque atherosclerosis, chronic kidney disease, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and pulmonary fibrosis. Conclusion: SET7/9 is an important methyltransferase, which can catalyze the methylation of a variety of proteins. Its substrates are closely related to the occurrence and development of tumors.

Transdermal Drug delivery: A step towards treatment of cancer

Background: Transdermal drug delivery is an emerging and tempting system over oral and hypodermic drug delivery system. With the new developments in skin penetration techniques, anticancer drugs ranging from hydrophilic macromolecules to lipophilic drugs can be administered via transdermal route to treat cancer. Objective: In the present review, various approaches to enhance the transdermal delivery of drugs is discussed including the micro and nanotechnology based transdermal formulations like chemotherapy, gene therapy, immunotherapy, phototherapy, vaccines and medical devices. Limitations and advantages of various transdermal technologies is also elaborated. Method: In this review, patent applications and recent literature of transdermal drug delivery systems employed to cure mainly cancer are covered. Results: Transdermal drug delivery systems have proved their potential to cure cancer. They increase the bioavailability of drug by site specific drug delivery and can reduce the side effects/toxicity associated with anticancer drugs. Conclusion: The potential of transdermal drug delivery systems to carry the drug may unclutter novel ways for therapeutic intercessions in various tumors.