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Life
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Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin
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Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (14 July 2023) | Viewed by 9130

Special Issue Editor

Dr. Dagmara Wróbel-Biedrawa

E-Mail Website
Guest Editor
Department of Clinical Pharmacy, Jagiellonian University, Krakow, Poland
Interests: plant-derived compounds; plant extracts; anti-cancer; anti-tumor; melanoma; anti-tyrosinase; neuropsychopharmacology; anti-inflammatory; behavioral testing; central nervous system; anxiolytic; anti-depressant; anti-psychotic
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The battle with non-communicable pandemics (e.g., cancer) is ongoing. According to WHO data, cancer is one of the leading causes of death in upper-middle-income and high-income countries, and despite available therapies, many patients are still incurably ill and eventually die. Subsequently, there is a need for better chemotherapeutics with greater efficacy and lower side-effect-evoking potential. Furthermore, we are increasingly aware of the role of inflammation in the pathogenesis of many diseases (e.g., cancer, metabolic or psychiatric diseases). Today, we realize that it is vital to provide substances with anti-inflammatory activity, either as a basic or additional mechanism of action.

The hope of an answer to the unmet desire for more efficient therapies lies within the science, and in the efforts of systematic and laborious research. Equally important are basic investigations that explain the background, cause and effect relationships in the pathogenesis of diseases, and investigations of substances that can be implemented at different stages and sites of the described processes.

One of the trends in searching for new therapeutics is to return to Nature. Plants are parts of the same global ecosystem as humans, and try to defend themselves to survive as well. Thus, we can learn and draw inspiration from them, as they are still winning in the evolutionary race.

Taking all the aforementioned into account, in this Special Issue we aim to collect the latest data on cytotoxic, anti-tumor and anti-inflammatory agents of natural origin—especially plant-derived agents—creating an updated source of information in the field of science that is changing very quickly because of the enormous accumulation of new data.

Dr. Dagmara Wróbel-Biedrawa
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • neoplasm
  • inflammation
  • cytotoxic
  • anti-tumor
  • anti-inflammatory
  • plant
  • natural origin

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Published Papers (5 papers)

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Research

14 pages, 3333 KiB  
Article
Antimicrobial, Cytotoxic, and α-Glucosidase Inhibitory Activities of Ethanol Extract and Chemical Constituents Isolated from Homotrigona apicalis Propolis—In Vitro and Molecular Docking Studies
by Diep Thi Lan Phuong, Nguyen Van Phuong, Nguyen Le Tuan, Nguyen Thanh Cong, Nguyen Thu Hang, Le Nguyen Thanh, Vu Thi Hue, Nguyen Quoc Vuong, Nguyen Thi Thu Ha, Milena Popova, Boryana Trusheva and Vassya Bankova
Life 2023, 13(8), 1682; https://doi.org/10.3390/life13081682 - 3 Aug 2023
Cited by 3 | Viewed by 1848
Abstract
The chemical investigation of Homotrigona apicalis propolis collected in Binh Dinh province, Vietnam, led to the isolation of nine compounds, including four sesquiterpenes: spathulenol (1), 1αH,5βH-aromandendrane-4β,10α-diol (2), 1β,6α [...] Read more.
The chemical investigation of Homotrigona apicalis propolis collected in Binh Dinh province, Vietnam, led to the isolation of nine compounds, including four sesquiterpenes: spathulenol (1), 1αH,5βH-aromandendrane-4β,10α-diol (2), 1β,6α-dihydroxy-4(15)-eudesmene (3), and 1βH,5βH-aromandendrane-4α,10β-diol (4); three triterpenes: acetyl oleanolic acid (5), 3α-hydroxytirucalla-8,24-dien-21-oic acid (6), and ursolic acid (7); and two xanthones: cochinchinone A (8) and α-mangostin (9). Sesquiterpens 1–4 and triterpene 6 were isolated for the first time from stingless bee propolis. Plants in the Cratoxylum and Aglaia genus were suggested as resin sources of the propolis sample. In the antibacterial activity evaluation, the EtOH extract only showed moderate activity on S. aureus, while the isolated compounds 7–9 showed good antibacterial activity, with IC50 values of 0.56 to 17.33 µg/mL. The EtOH extract displayed selective cytotoxicity against the A-549 cancer cell line, with IC50 values of 22.82 ± 0.86 µg/mL, and the xanthones 8 and 9 exhibited good activity against the KB, HepG-2, and A-549 cancer cell lines, with IC50 values ranging from 7.55 ± 0.25 µg/mL to 29.27 ± 2.07 µg/mL. The cytotoxic effects of xanthones 8 and 9 were determined by the inhibition of the EGFR and HER2 pathways using a molecular docking study. Compounds 8 and 9 displayed strong binding affinity with EFGR and HER2, with values of −9.3 to −9.9 kcal/mol. Compounds 5, 8, and 9 showed potential α-glucosidase inhibitory activities, which were further confirmed by computational studies. The binding energies of compounds 5, 8, and 9 were lower than that of arcabose. Full article
(This article belongs to the Special Issue Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin)
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23 pages, 6372 KiB  
Article
Methoxylated Cinnamic Esters with Antiproliferative and Antimetastatic Effects on Human Lung Adenocarcinoma Cells
by João Graciano Sampaio, Carolina Girotto Pressete, Adilson Vidal Costa, Felipe Terra Martins, Graziela Domingues de Almeida Lima, Marisa Ionta and Róbson Ricardo Teixeira
Life 2023, 13(7), 1428; https://doi.org/10.3390/life13071428 - 22 Jun 2023
Cited by 1 | Viewed by 1325
Abstract
Lung cancer is the leading cause of cancer mortality worldwide, and malignant melanomas are highly lethal owing to their elevated metastatic potential. Despite improvements in therapeutic approaches, cancer treatments are not completely effective. Thus, new drug candidates are continuously sought. We synthesized mono- [...] Read more.
Lung cancer is the leading cause of cancer mortality worldwide, and malignant melanomas are highly lethal owing to their elevated metastatic potential. Despite improvements in therapeutic approaches, cancer treatments are not completely effective. Thus, new drug candidates are continuously sought. We synthesized mono- and di-methoxylated cinnamic acid esters and investigated their antitumor potential. A cell viability assay was performed to identify promising substances against A549 (non-small-cell lung cancer) and SK-MEL-147 (melanoma) cells. (E)-2,5-dimethoxybenzyl 3-(4-methoxyphenyl)acrylate (4m), a monomethoxylated cinnamic acid derivative, was identified as the lead antitumor compound, and its antitumor potential was deeply investigated. Various approaches were employed to investigate the antiproliferative (clonogenic assay and cell cycle analysis), proapoptotic (annexin V assay), and antimigratory (wound-healing and adhesion assays) activities of 4m on A549 cells. In addition, western blotting was performed to explore its mechanism of action. We demonstrated that 4m inhibits the proliferation of A549 by promoting cyclin B downregulation and cell cycle arrest at G2/M. Antimigratory and proapoptotic activities of 4m on A549 were also observed. The antitumor potential of 4m involved its ability to modulate the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway once phosphorylated-ERK expression was considerably reduced in response to treatment. Our findings demonstrate that 4m is a promising anticancer drug candidate. Full article
(This article belongs to the Special Issue Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin)
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16 pages, 8503 KiB  
Article
Discovering Potential Anti-Oral Squamous Cell Carcinoma Mechanisms from Kochiae Fructus Using Network-Based Pharmacology Analysis and Experimental Validation
by Youn-Sook Kim, Jin-Choon Lee, Minhyung Lee, Hae-Jin Oh, Won G. An and Eui-Suk Sung
Life 2023, 13(6), 1300; https://doi.org/10.3390/life13061300 - 31 May 2023
Cited by 1 | Viewed by 1490
Abstract
The natural product Kochiae Fructus (KF) is the ripe fruit of Kochia scoparia (L.) Schrad and is renowned for its anti-inflammatory, anticancer, anti-fungal, and anti-pruritic effects. This study examined the anticancer effect of components of KF to assess its potential as an adjuvant [...] Read more.
The natural product Kochiae Fructus (KF) is the ripe fruit of Kochia scoparia (L.) Schrad and is renowned for its anti-inflammatory, anticancer, anti-fungal, and anti-pruritic effects. This study examined the anticancer effect of components of KF to assess its potential as an adjuvant for cancer treatment. Network-based pharmacological and docking analyses of KF found associations with oral squamous cell carcinoma. The molecular docking of oleanolic acid (OA) with LC3 and SQSTM1 had high binding scores, and hydrogen binding with amino acids of the receptors suggests that OA is involved in autophagy, rather than the apoptosis pathway. For experimental validation, we exposed SCC-15 squamous carcinoma cells derived from a human tongue lesion to KF extract (KFE), OA, and cisplatin. The KFE caused SCC-15 cell death, and induced an accumulation of the autophagy marker proteins LC3 and p62/SQSTM1. The novelty of this study lies in the discovery that the change in autophagy protein levels can be related to the regulatory death of SCC-15 cells. These findings suggest that KF is a promising candidate for future studies to provide insight into the role of autophagy in cancer cells and advance our understanding of cancer prevention and treatment. Full article
(This article belongs to the Special Issue Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin)
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11 pages, 2119 KiB  
Article
Towards Non-Invasive Intravital Microscopy: Advantages of Using the Ear Lobe Instead of the Cremaster Muscle
by Iara Mota-Silva, Miguel A. R. B. Castanho and Ana Santos Silva-Herdade
Life 2023, 13(4), 887; https://doi.org/10.3390/life13040887 - 27 Mar 2023
Viewed by 1579
Abstract
Inflammation is essential in the protection of the organism and wound repair, but in cases of chronic inflammation can also cause microvasculature deterioration. Thus, inflammation monitorization studies are important to test potential therapeutics. The intravital microscopy (IVM) technique monitors leukocyte trafficking in vivo, [...] Read more.
Inflammation is essential in the protection of the organism and wound repair, but in cases of chronic inflammation can also cause microvasculature deterioration. Thus, inflammation monitorization studies are important to test potential therapeutics. The intravital microscopy (IVM) technique monitors leukocyte trafficking in vivo, being a commonly used procedure to report systemic conditions. Although the cremaster muscle, an established protocol for IVM, may affect the hemodynamics because of its surgical preparation, only male animals are used, and longitudinal studies over time are not feasible. Thinking how this impacts future studies, our aim is to understand if the IVM technique can be successfully performed using the ear lobe instead of the cremaster muscle. Elevated IL-1β plasmatic concentrations confirmed the systemic inflammation developed in a diabetic animal model, while the elevated number of adherent and rolling leukocytes in the ear lobe allowed for the same conclusion. Thus, this study demonstrates that albeit its thickness, the ear lobe protocol for IVM is efficient, non-invasive, more reliable, cost-effective and timesaving. Full article
(This article belongs to the Special Issue Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin)
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15 pages, 9327 KiB  
Article
Defining the Potential Targets for Biological Activity of Isoegomaketone Based on Network Pharmacology and Molecular Docking Methods
by Juzhao Zhang, Ruo Wang, Yuxuan Qin and Chengling Feng
Life 2022, 12(12), 2115; https://doi.org/10.3390/life12122115 - 15 Dec 2022
Cited by 3 | Viewed by 2063
Abstract
Isoegomaketone is a water-soluble natural ketone compound that is commonly present in Rabdosia angustifolia and Perilla frutescens. At present, it is known that isoegomaketone has a wide range of pharmacological activity, but there has been no thorough investigation of its potential targets. [...] Read more.
Isoegomaketone is a water-soluble natural ketone compound that is commonly present in Rabdosia angustifolia and Perilla frutescens. At present, it is known that isoegomaketone has a wide range of pharmacological activity, but there has been no thorough investigation of its potential targets. As a result, we examined the potential targets of isoegomaketone using the network pharmacology approach. In our study, the TCM Database@Taiwan was utilized to search for the chemical formula. The pharmacological characteristics of isoegomaketone were then evaluated in silico using the Swiss Absorption, Distribution, Metabolism, and Excretion (Swiss ADME) and Deep Learning–Acute Oral Toxicity (DL-AOT) methods, and the potential isoegomaketone target genes were identified using a literature study. Additionally, using the clusterProfiler R package 3.8.1, the Gene Ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of target genes were performed. In order to obtain the protein interaction network, we simultaneously submitted the targets to the STRING database. After this, we performed molecular docking with respect to targets and isoegomaketone. Finally, we created visual networks of protein–protein interactions (PPI) and examined these networks. Our results showed that isoegomaketone had good drug-likeness, bioavailability, medicinal chemistry friendliness, and acceptable toxicity. Subsequently, through the literature analysis, 48 target genes were selected. The bioinformatics analysis and network analysis found that these target genes were closely related to the biological processes of isoegomaketone, such as atherosclerotic formation, inflammation, tumor formation, cytotoxicity, bacterial infection, virus infection, and parasite infection. These findings show that isoegomaketone may interact with a wide range of proteins and biochemical processes to form a systematic pharmacological network, which has good value for the creation and use of drugs. Full article
(This article belongs to the Special Issue Emerging Cytotoxic, Anti-tumor and Anti-inflammatory Bioactive Compounds of Natural Origin)
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