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Anticancer Compounds in Medicinal Plants — In Honour of the...
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Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (17 May 2024) | Viewed by 4309

Special Issue Editors

Dr. Paulo Santos

E-Mail Website1 Website2
Guest Editor
Department of Chemistry and Chemistry Center—Vila Real (CQ-VR), School of Life and Environmental Sciences, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
Interests: organic synthesis; functional dyes; structural elucidation; natural products chemistry; medicinal plants; natural bioactive compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Lillian Barros

grade E-Mail Website1 Website2
Guest Editor
Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
Interests: natural bioactive compounds; medicinal chemistry; bioactivity and toxicology; functional applications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer, in its multiple forms, is presently one of the leading causes of death in both developing and developed countries and it has become a major health problem and a burden for most public health care systems worldwide. Although several decades of drug discovery and development have provided a number of useful chemotherapeutic agents, there is a continuous interest in the search for new chemical entities with improved anticancer effectiveness and safety.

Since ancient times, humankind has relied on herbal medicines for the treatment and prevention of a plethora of different ailments and their beneficial properties have been recognized both by traditional medicines and more contemporary herbalism practices. Medicinal plants, which have contributed to the collection of compounds that are now at our disposal for cancer therapy, constitute a reservoir of natural products that are able to provide new molecules with anticancer activity and new molecular frameworks that have inspired the design of derivatives with improved therapeutic ability. As plant-derived compounds are often devoid of cytotoxicity to normal human cells, the attention of scientific research has been increasingly driven towards natural compounds, as they may represent a source of anticancer molecules with less toxic side effects compared to current chemotherapeutic drugs.

This Special Issue “Anticancer Compounds in Medicinal Plants” invites researchers to contribute with original research or review articles related to natural compounds with anticancer properties isolated from medicinal plants. The contributions include the discovery of new compounds, the in vitro and in vivo assessment of the anticancer properties of medicinal plant-derived compounds, as well as the elucidation of their mechanisms of action and the design of derivatives with improved efficacy.

Dr. Paulo Santos
Dr. Lillian Barros
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Pharmaceuticals 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 2900 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

  • natural products
  • phytochemicals
  • cancer
  • secondary metabolites
  • medicinal plants

Published Papers (7 papers)

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Research

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21 pages, 4514 KiB  
Article
Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings
by Jurandy do Nascimento Silva, José Ivo Araújo Beserra Filho, Boris Timah Acha, Fernanda Regina de Castro Almeida, Emanuelle Karine Frota Batista, Valdenizia Rodrigues Silva, Larissa Mendes Bomfim, Milena Botelho Pereira Soares, Daniel Pereira Bezerra, André Gonzaga dos Santos, Francisco das Chagas Pereira de Andrade, Anderson Nogueira Mendes, Daniel Dias Rufino Arcanjo and Paulo Michel Pinheiro Ferreira
Pharmaceuticals 2024, 17(5), 633; https://doi.org/10.3390/ph17050633 - 14 May 2024
Viewed by 223
Abstract
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or [...] Read more.
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12–39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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21 pages, 12762 KiB  
Article
β-Elemene Reverses Gefitinib Resistance in NSCLC Cells by Inhibiting lncRNA H19-Mediated Autophagy
by Ruonan Zhang, Yintao Zheng, Qianru Zhu, Xiaoqing Gu, Bo Xiang, Xidong Gu, Tian Xie and Xinbing Sui
Pharmaceuticals 2024, 17(5), 626; https://doi.org/10.3390/ph17050626 - 14 May 2024
Viewed by 255
Abstract
Lung cancer is a leading cause of mortality worldwide, especially among Asian patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Initially, first-generation EGFR tyrosine kinase inhibitors (TKIs) are commonly administered as the primary treatment option; however, [...] Read more.
Lung cancer is a leading cause of mortality worldwide, especially among Asian patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Initially, first-generation EGFR tyrosine kinase inhibitors (TKIs) are commonly administered as the primary treatment option; however, encountering resistance to these medications poses a significant obstacle. Hence, it has become crucial to address initial resistance and ensure continued effectiveness. Recent research has focused on the role of long noncoding RNAs (lncRNAs) in tumor drug resistance, especially lncRNA H19. β-elemene, derived from Curcuma aromatic Salisb., has shown strong anti-tumor effects. However, the relationship between β-elemene, lncRNA H19, and gefitinib resistance in NSCLC is unclear. This study aims to investigate whether β-elemene can enhance the sensitivity of gefitinib-resistant NSCLC cells to gefitinib and to elucidate its mechanism of action. The impact of gefitinib and β-elemene on cell viability was evaluated using the cell counting kit-8 (CCK8) assay. Furthermore, western blotting and qRT-PCR analysis were employed to determine the expression levels of autophagy-related proteins and genes, respectively. The influence on cellular proliferation was gauged through a colony-formation assay, and apoptosis induction was quantified via flow cytometry. Additionally, the tumorigenic potential in vivo was assessed using a xenograft model in nude mice. The expression levels of LC3B, EGFR, and Rab7 proteins were examined through immunofluorescence. Our findings elucidate that the resistance to gefitinib is intricately linked with the dysregulation of autophagy and the overexpression of lncRNA H19. The synergistic administration of β-elemene and gefitinib markedly attenuated the proliferative capacity of resistant cells, expedited apoptotic processes, and inhibited the in vivo proliferation of lung cancer. Notably, β-elemene profoundly diminished the expression of lncRNA H19 and curtailed autophagic activity in resistant cells, thereby bolstering their responsiveness to gefitinib. Moreover, β-elemene disrupted the Rab7-facilitated degradation pathway of EGFR, facilitating its repositioning to the plasma membrane. β-elemene emerges as a promising auxiliary therapeutic for circumventing gefitinib resistance in NSCLC, potentially through the regulation of lncRNA H19-mediated autophagy. The participation of Rab7 in this dynamic unveils novel insights into the resistance mechanisms operative in lung cancer, paving the way for future therapeutic innovations. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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13 pages, 2355 KiB  
Article
Comprehensive Chemical Profiling and Mechanistic Insight into Anticancer Activity of Annona muricata Leaves Extract
by Rehab H. Abdallah, Al-sayed R. Al-Attar, Youssef M. Shehata, Doaa M. Abdel-Fattah, Rahnaa M. Atta, Omer I. Fantoukh and Ahmed M. Mustafa
Pharmaceuticals 2024, 17(5), 614; https://doi.org/10.3390/ph17050614 - 10 May 2024
Viewed by 404
Abstract
The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract’s impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity [...] Read more.
The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract’s impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity of the phytochemical constituents of the aqueous leaf capsule extract and their impacts on EAC as anticancer agents. The UPLC-ESI-MS/MS screening resulted in 410 tentatively identified metabolites. Among them, 384 compounds were tentatively identified in a previous study, besides a number of 26 compounds belonging to acetogenins, phenolics, flavonoids, alkaloids, and other miscellaneous compounds, which were exclusively identified in the aqueous extract of the leaf capsule. Interestingly, a new compound was tentatively characterized as galloyl-quinic acid-rutinoside. This study also demonstrated that treating EAC mice with an extract from A. muricata leaves significantly improved the abnormalities in the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes. Furthermore, the extract showed good protection against induced Ehrlich hepatocarcinoma, according to the microscopical, histological, and immune-histochemical analyses of the liver tissues and tumor mass. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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13 pages, 3026 KiB  
Article
Torenia sp. Extracts Contain Multiple Potent Antitumor Compounds with Nematocidal Activity, Triggering an Activated DNA Damage Checkpoint and Defective Meiotic Progression
by Qinghao Meng, Robert P. Borris and Hyun-Min Kim
Pharmaceuticals 2024, 17(5), 611; https://doi.org/10.3390/ph17050611 - 10 May 2024
Viewed by 304
Abstract
Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and [...] Read more.
Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and disrupted meiotic progression, thus disrupting developmental processes. Notably, Torenia sp. extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, hindering germline development. LC–MS analysis revealed 13 compounds in the Torenia sp. extracts, including flavonoids, terpenoids, tanshinones, an analog of resveratrol, iridoids, carotenoids, fatty acids, and alkaloids. Of these, 10 are known for their antitumor activity, suggesting the potential of Torenia species beyond traditional gardening, extending into pharmaceutical and therapeutic applications. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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13 pages, 1851 KiB  
Article
Static Magnetic Field Reduces the Anticancer Effect of Hinokitiol on Melanoma Malignant Cells—Gene Expression and Redox Homeostasis Studies
by Agnieszka Synowiec-Wojtarowicz, Agata Krawczyk and Magdalena Kimsa-Dudek
Pharmaceuticals 2024, 17(4), 430; https://doi.org/10.3390/ph17040430 - 27 Mar 2024
Viewed by 737
Abstract
Background: Melanoma malignant is characterized by a high mortality rate, accounting for as much as 65% of deaths caused by skin cancer. A potential strategy in cancer treatment may be the use of natural compounds, which include hinokitiol (β-Thujaplicin), a phenolic component of [...] Read more.
Background: Melanoma malignant is characterized by a high mortality rate, accounting for as much as 65% of deaths caused by skin cancer. A potential strategy in cancer treatment may be the use of natural compounds, which include hinokitiol (β-Thujaplicin), a phenolic component of essential oils extracted from cypress trees. Many studies confirm that a high-induction SMF (static magnetic field) has anticancer effects and can be used as a non-invasive anticancer therapy in combination with or without drugs. Aim: The aim of this experiment was to evaluate the effect of a static magnetic field on melanoma cell cultures (C32 and COLO 829) treated with hinokitiol. Methods and Results: Melanoma cells were exposed to a static magnetic field of moderate induction and hinokitiol. The research included determining the activity of the antioxidant enzymes (SOD, GPx, and CAT) and MDA concentration as well as the gene expression profile. Conclusion: Hinokitiol disturbs the redox homeostasis of C32 and COLO 829 melanoma malignant cells. Moreover, a static magnetic field has a protective effect on melanoma malignant cells and abolishes the anticancer effect of hinokitiol. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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20 pages, 4816 KiB  
Article
Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport
by Chung-Pu Wu, Megumi Murakami, Yen-Ching Li, Yang-Hui Huang, Yu-Tzu Chang, Tai-Ho Hung, Yu-Shan Wu and Suresh V. Ambudkar
Pharmaceuticals 2023, 16(11), 1595; https://doi.org/10.3390/ph16111595 - 12 Nov 2023
Viewed by 1149
Abstract
The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer [...] Read more.
The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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Review

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36 pages, 7182 KiB  
Review
Exploring Synergistic Interactions between Natural Compounds and Conventional Chemotherapeutic Drugs in Preclinical Models of Lung Cancer
by Mihaela Boța, Lavinia Vlaia, Alex-Robert Jîjie, Iasmina Marcovici, Flavia Crişan, Cristian Oancea, Cristina Adriana Dehelean, Tudor Mateescu and Elena-Alina Moacă
Pharmaceuticals 2024, 17(5), 598; https://doi.org/10.3390/ph17050598 - 8 May 2024
Viewed by 481
Abstract
In the current work, the synergy between natural compounds and conventional chemotherapeutic drugs is comprehensively reviewed in light of current preclinical research findings. The prognosis for lung cancer patients is poor, with a 5-year survival rate of 18.1%. The use of natural compounds [...] Read more.
In the current work, the synergy between natural compounds and conventional chemotherapeutic drugs is comprehensively reviewed in light of current preclinical research findings. The prognosis for lung cancer patients is poor, with a 5-year survival rate of 18.1%. The use of natural compounds in combination with conventional chemotherapeutic drugs has gained significant attention as a potential novel approach in the treatment of lung cancer. The present work highlights the importance of finding more effective therapies to increase survival rates. Chemotherapy is a primary treatment option for lung cancer but it has limitations such as reduced effectiveness because cancer cells become resistant. Natural compounds isolated from medicinal plants have shown promising anticancer or chemopreventive properties and their synergistic effect has been observed when combined with conventional therapies. The combined use of an anti-cancer drug and a natural compound exhibits synergistic effects, enhancing overall therapeutic actions against cancer cells. In conclusion, this work provides an overview of the latest preclinical research on medicinal plants and plant-derived compounds as alternative or complementary treatment options for lung cancer chemotherapy and discusses the potential of natural compounds in treating lung cancer with minimal side effects. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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