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Plant-Derived Targeted Strategies in Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 45175

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Special Issue Editors

Dr. Konstantina Karamanou

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Guest Editor

Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece
Interests: small leucine rich proteoglycans; breast cancer, melanoma; cell biology; cell signaling

Dr. Stamatis Rigas

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Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece
Interests: abiotic stress; root development; selective proteolysis; arabidopsis genetics

Prof. Dr. Polydefkis Hatzopoulos

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Laboratory of Molecular Biology, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece
Interests: molecular biology; plant biotechnology; developmental genetics; abiotic stress and adaptation
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Dear Colleagues,

Cancer is a multifactorial disease, characterized by uncontrolled cell growth and acquisition of metastatic properties. Recently, remarkable advances in anticancer therapy have involved the use of many compounds of herbal origin or structural analogues derived from them. Medicinal plants constitute a reservoir of active ingredients able to provide new molecules with anticancer activity and new molecular frameworks capable of inspiring the design of derivatives with improved therapeutic properties. Many natural products of plant origin have already been isolated and characterized, although the molecular mechanisms underlying their therapeutic effects remain unexplored.

Secondary metabolites of higher plants also constitute an alternative strategy for cancer treatment, as they exert numerous effects on tumorigenesis, both in vitro and in vivo, interact with anticancer drugs, thus positively or negatively affecting their efficacy, and protect normal tissues of the host organism against adverse effects of anticancer therapies. The attention of scientific research has been increasingly driven toward natural compounds, as they may represent a source of anticancer molecules with less toxic side effects compared to current chemotherapeutic drugs. The field of plant-derived cancer approaches is constantly evolving, and therefore, a Special Issue on plant-derived anticancer compounds is opportune and even imperative.

We cordially invite researchers to submit up-to-date original research articles, and comprehensive review articles on the topic highlighted in this Special Issue of Cancers, “Plant-Derived Targeted Strategies in Cancer’’. The contributions should include the state of the art in the field of anticancer agents of plant origin, the discovery of new compounds, in vitro and in vivo assessment of their anticancer properties, as well as the elucidation of their mechanisms of action and the design of derivatives with improved efficacy. The Special Issue also targets novel biotechnological approaches of the production of plant-derived promising anticancer agents, biosynthesis mode of action, elicitation, and pharmacokinetics of these anticancer compounds. Up-to-date studies on the metabolites and their perspective enzymes, to decipher their transcriptomics, proteomics, and metabolomics regulation mechanisms can also be included.

Dr. Konstantina Karamanou
Dr. Stamatis Rigas
Prof. Dr. Polydefkis Hatzopoulos
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 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.

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Keywords

plant substances
medicinal plants
secondary metabolites
microbiota and cancer
pharmacological interactions
natural products
preclinical and clinical trials in cancer
molecular mechanisms
anticancer therapy

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Published Papers (8 papers)

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Research

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16 pages, 3318 KiB

Open AccessArticle

The Sesquiterpene Lactone-Rich Fraction of Inula helenium L. Enhances the Antitumor Effect of Anti-PD-1 Antibody in Colorectal Cancer: Integrative Phytochemical, Transcriptomic, and Experimental Analyses

by Jaemoo Chun, Sang-Min Park, Minsung Lee, In Jin Ha and Mi-Kyung Jeong

Cancers 2023, 15(3), 653; https://doi.org/10.3390/cancers15030653 - 20 Jan 2023

Cited by 6 | Viewed by 3046

Abstract

Treatment strategies combining immune checkpoint inhibitors with sesquiterpene lactones have attracted much attention as a promising approach for cancer treatment. We systemically analyzed gene expression profiles of cells in response to two major sesquiterpene lactones, alantolactone and isoalantolactone, and determined whether the sesquiterpene lactone-rich fraction of Inula helenium L. (SFIH) enhances the antitumor effect of anti-PD-1 antibody in MC38 colorectal cancer-bearing mice. Gene expression and pathway analysis using RNA sequencing data were used to identify the SFIH-driven combined activity with anti-PD-1 antibody. The results showed that SFIH significantly enhanced the antitumor effect of anti-PD-1 antibody by reducing tumor growth and increasing the survival time of mice. Specifically, SFIH exhibited antitumor activity when combined with anti-PD-1 antibody, and the effects were further enhanced compared with monotherapy. An analysis of immune cells indicated that combination treatment with SFIH and anti-PD-1 antibody significantly increased the proportion of CD8⁺ T cells. Moreover, combination treatment enhanced antitumor immunity by decreasing the population of myeloid-derived suppressor cells and increasing the number of M1-like macrophages. Pathway enrichment analysis revealed that combination therapy activated immune-related pathways to a greater extent than monotherapy. In conclusion, our integrative analysis demonstrates that SFIH enhances the response of murine tumors to anti-PD-1 antibody. These findings provide insight into developing integrative therapeutics and molecular data for the use of natural products as an adjunct treatment for colorectal cancer. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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16 pages, 3414 KiB

Open AccessArticle

Cytotoxic Mechanism of Momilactones A and B against Acute Promyelocytic Leukemia and Multiple Myeloma Cell Lines

by La Hoang Anh, Vu Quang Lam, Akiyoshi Takami, Tran Dang Khanh, Nguyen Van Quan and Tran Dang Xuan

Cancers 2022, 14(19), 4848; https://doi.org/10.3390/cancers14194848 - 4 Oct 2022

Cited by 8 | Viewed by 2741

Abstract

This is the first study clarifying the cytotoxic mechanism of momilactones A (MA) and B (MB) on acute promyelocytic leukemia (APL) HL-60 and multiple myeloma (MM) U266 cell lines. Via the MTT test, MB and the mixture MAB (1:1, w/w) exhibit a potent cytotoxicity on HL-60 (IC₅₀ = 4.49 and 4.61 µM, respectively), which are close to the well-known drugs doxorubicin, all-trans retinoic acid (ATRA), and the mixture of ATRA and arsenic trioxide (ATRA/ATO) (1:1, w/w) (IC₅₀ = 5.22, 3.99, and 3.67 µM, respectively). Meanwhile MB, MAB, and the standard suppressor doxorubicin substantially inhibit U266 (IC₅₀ = 5.09, 5.59, and 0.24 µM, respectively). Notably, MB and MAB at 5 µM may promote HL-60 and U266 cell apoptosis by activating the phosphorylation of p-38 in the mitogen-activated protein kinase (MAPK) pathway and regulating the relevant proteins (BCL-2 and caspase-3) in the mitochondrial pathway. Besides, these compounds may induce G2 phase arrest in the HL-60 cell cycle through the activation of p-38 and disruption of CDK1 and cyclin B1 complex. Exceptionally, momilactones negligibly affect the non-cancerous cell line MeT-5A. This finding provides novel insights into the anticancer property of momilactones, which can be a premise for future studies and developments of momilactone-based anticancer medicines. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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16 pages, 9923 KiB

Open AccessArticle

A Novel Plant-Derived Choline Transporter-like Protein 1 Inhibitor, Amb544925, Induces Apoptotic Cell Death via the Ceramide/Survivin Pathway in Tongue Squamous Cell Carcinoma

by Kaoru Shibata, Nozomi Nishijima, Kaho Hirai, Saiichiro Watanabe, Tsuyoshi Yamanaka, Daichi Chikazu and Masato Inazu

Cancers 2022, 14(2), 329; https://doi.org/10.3390/cancers14020329 - 10 Jan 2022

Cited by 6 | Viewed by 2688

Abstract

Background: Despite recent advances in the early detection and treatment of TSCC patients, recurrence rates and survival rates have not improved. The high frequency of lymph node metastasis is one of the causes, and the drug development of new therapeutic mechanisms such as metastasis control is desired. Choline transporter-like protein 1 (CTL1) has attracted attention as a target molecule in cancer therapy. In this study, we examined the antitumor effects of Amb544925, a plant-derived CTL1 inhibitor. Methods: The TSCC cell line HSC-3 was used to measure [³H]choline uptake, cell survival, caspase activity, and cell migration. Xenograft model mice were prepared to verify the antitumor effect of Amb544925. Results: Amb544925 inhibited cell viability and increased caspase-3/7 activity at concentrations that inhibited choline uptake. Amb544925 and ceramide increased SMPD4 expression and suppressed surivivin expression. Furthermore, Amb544925 and ceramide inhibited the migration of HSC-3 cells. In the xenograft model mice, Amb544925 suppressed tumor growth and CTL1 mRNA expression. Conclusions: The plant-derived CTL1 inhibitor Amb544925 is a lead compound of a new anticancer agent exhibiting antitumor effects and inhibition of cell migration through the ceramide/survivin pathway. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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23 pages, 4713 KiB

Open AccessReview

Natural Products/Bioactive Compounds as a Source of Anticancer Drugs

by Syeda Tasmia Asma, Ulas Acaroz, Kálmán Imre, Adriana Morar, Syed Rizwan Ali Shah, Syed Zajif Hussain, Damla Arslan-Acaroz, Hayri Demirbas, Zehra Hajrulai-Musliu, Fatih Ramazan Istanbullugil, Ali Soleimanzadeh, Dmitry Morozov, Kui Zhu, Viorel Herman, Abdelhanine Ayad, Christos Athanassiou and Sinan Ince

Cancers 2022, 14(24), 6203; https://doi.org/10.3390/cancers14246203 - 15 Dec 2022

Cited by 77 | Viewed by 9040

Abstract

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants and microbial species are chosen based on their composition, ecology, phytochemical, and ethnopharmacological properties. Plants and their derivatives have played a significant role in producing effective anticancer agents. Some plant derivatives include vincristine, vinblastine, irinotecan, topotecan, etoposide, podophyllotoxin, and paclitaxel. Based on their particular activity, a number of other plant-derived bioactive compounds are in the clinical development phase against cancer, such as gimatecan, elomotecan, etc. Additionally, the conjugation of natural compounds with anti-cancerous drugs, or some polymeric carriers particularly targeted to epitopes on the site of interest to tumors, can generate effective targeted treatment therapies. Cognizance from such pharmaceutical research studies would yield alternative drug development strategies through natural sources which could be economical, more reliable, and safe to use. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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80 pages, 17778 KiB

Open AccessReview

New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways

by Alma Martelli, Marzieh Omrani, Maryam Zarghooni, Valentina Citi, Simone Brogi, Vincenzo Calderone, Antoni Sureda, Shahrokh Lorzadeh, Simone C. da Silva Rosa, Beniamin Oscar Grabarek, Rafał Staszkiewicz, Marek J. Los, Seyed Fazel Nabavi, Seyed Mohammad Nabavi, Parvaneh Mehrbod, Daniel J. Klionsky and Saeid Ghavami

Cancers 2022, 14(23), 5839; https://doi.org/10.3390/cancers14235839 - 26 Nov 2022

Cited by 22 | Viewed by 4830

Abstract

Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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42 pages, 1949 KiB

Open AccessReview

Hidden in Plants—A Review of the Anticancer Potential of the Solanaceae Family in In Vitro and In Vivo Studies

by Tomasz Kowalczyk, Anna Merecz-Sadowska, Patricia Rijo, Mattia Mori, Sophia Hatziantoniou, Karol Górski, Janusz Szemraj, Janusz Piekarski, Tomasz Śliwiński, Michał Bijak and Przemysław Sitarek

Cancers 2022, 14(6), 1455; https://doi.org/10.3390/cancers14061455 - 11 Mar 2022

Cited by 25 | Viewed by 6483

Abstract

Many of the anticancer agents that are currently in use demonstrate severe side effects and encounter increasing resistance from the target cancer cells. Thus, despite significant advances in cancer therapy in recent decades, there is still a need to discover and develop new, alternative anticancer agents. The plant kingdom contains a range of phytochemicals that play important roles in the prevention and treatment of many diseases. The Solanaceae family is widely used in the treatment of various diseases, including cancer, due to its bioactive ingredient content. The purpose of this literature review is to highlight the antitumour activity of Solanaceae extracts—single isolated compounds and nanoparticles with extracts—and their synergistic effect with chemotherapeutic agents in various in vitro and in vivo cancer models. In addition, the biological properties of many plants of the Solanaceae family have not yet been investigated, which represents a challenge and an opportunity for future anticancer therapy. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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31 pages, 1644 KiB

Open AccessReview

Orchidaceae-Derived Anticancer Agents: A Review

by Tomasz Śliwiński, Tomasz Kowalczyk, Przemysław Sitarek and Marta Kolanowska

Cancers 2022, 14(3), 754; https://doi.org/10.3390/cancers14030754 - 31 Jan 2022

Cited by 18 | Viewed by 5498

Abstract

Species of orchids, which belong to the largest family of flowering plants, are commonly used in folk medicine for the treatment of infections and tumors. However, little is known about the actual chemical composition of these plants and their anticancer properties. In this paper, the most recent literature on orchid-derived bioactive substances with anticancer properties is reviewed. For the assessment, previous papers on the anticancer activity of Orchidaceae published since 2015 were considered. The papers were found by exploring electronic databases. According to the available data, many species of orchids contain potential antitumor chemicals. The bioactive substances in a relatively insignificant number of orchids are identified, and most studies are on Asian taxa. Broader research on American and African species and the correct identification of samples included in the experiments are essential for evaluating the usefulness of orchids as a plant family with vast anticancer potential. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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21 pages, 3401 KiB

Open AccessReview

Plant Derived Bioactive Compounds, Their Anti-Cancer Effects and In Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview

by Vijayakumar Shrihastini, Pandiyan Muthuramalingam, Sivakumar Adarshan, Mariappan Sujitha, Jen-Tsung Chen, Hyunsuk Shin and Manikandan Ramesh

Cancers 2021, 13(24), 6222; https://doi.org/10.3390/cancers13246222 - 10 Dec 2021

Cited by 46 | Viewed by 8446

Abstract

Cancer is one of the most common malignant diseases that occur worldwide, among which breast cancer is the second leading cause of death in women. The subtypes are associated with differences in the outcome and were selected for treatments according to the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor. Triple-negative breast cancer, one of the subtypes of breast cancer, is difficult to treat and can even lead to death. If breast cancer is not treated during the initial stages, it may spread to nearby organs, a process called metastasis, through the blood or lymph system. For in vitro studies, MCF-7, MDA-MB-231, MDA-MB-468, and T47B are the most commonly used breast cancer cell lines. Clinically, chemotherapy and radiotherapy are usually expensive and can also cause side effects. To overcome these issues, medicinal plants could be the best alternative for chemotherapeutic drugs with fewer side effects and cost-effectiveness. Furthermore, the genes involved in breast cancer can be regulated and synergized with signaling molecules to suppress the proliferation of breast cancer cells. In addition, nanoparticles encapsulating (nano-encapsulation) medicinal plant extracts showed a significant reduction in the apoptotic and cytotoxic activities of breast cancer cells. This present review mainly speculates an overview of the native medicinal plant derived anti-cancerous compounds with its efficiency, types and pathways involved in breast cancer along with its genes, the mechanism of breast cancer brain metastasis, chemoresistivity and its mechanism, bioinformatics approaches which could be an effective alternative for drug discovery. Full article

(This article belongs to the Special Issue Plant-Derived Targeted Strategies in Cancer)

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