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Natural Products Based Anticancer Drugs
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Natural Products Based Anticancer Drugs

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 10430

Special Issue Editors

Dr. Elżbieta Studzińska-Sroka

E-Mail Website
Guest Editor
Department of Pharmacognosy, Poznan University of Medical Sciences, 60-806 Poznan, Poland
Interests: natural compounds; plant extracts; medicinal plants; lichens; biological activity; phytochemistry; phytochemical drug analysis
Dr. Aleksandra Majchrzak-Celińska

E-Mail Website
Guest Editor
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland
Interests: brain tumors; glioblastoma; epigenetics; pharmacoepigenetics; biomarkers; Wnt/β-catenin pathway; phytocompounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Significant developments over the past century have led to lifestyle changes that have contributed to many diseases that seriously threaten health. Among them, cancer should be noted as one of the most common causes of death in the population worldwide. Despite the intensive development of medical science, there is still a lack of effective cancer treatments. It, therefore, becomes necessary to intensify the research that will bring tangible benefits to oncology therapy. 

The study of the anticancer potential of natural origin substances is a legitimate research direction. Indeed, plant-derived compounds, such as paclitaxel, vincristine, or those produced by the bacteria doxorubicin, are still used in treating various neoplasms. An increasing number of studies show that natural origin substances act by regulating molecular pathways, which are implicated in the growth and progression of cancer. Therefore, they represent a promising strategy to complement conventional cancer treatments.

This Special Issue aims to disseminate the results of research on natural origin substances (compounds and characterized extracts) that may be of legitimate importance in developing new drugs for antitumor therapy. The aim is to identify new agents against human cancers and evaluate their mechanisms of action. Research into new pharmaceutical formulations based on natural origin, anticancer, biologically active substances is also a valuable approach for the progress of novel anticancer drugs. Hence, we welcome original research and review articles focused on the anticancer potential of natural substances in regard to their use as an anticancer drug.

Dr. Elżbieta Studzińska-Sroka
Dr. Aleksandra Majchrzak-Celińska
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • anticancer drug development
  • natural compounds and extracts with anticancer properties
  • phytochemistry
  • mechanism-of-action evaluation
  • cell-based analyses
  • plant-based drug formulations

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Published Papers (5 papers)

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Research

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24 pages, 9184 KiB  
Article
Conofolidine: A Natural Plant Alkaloid That Causes Apoptosis and Senescence in Cancer Cells
by Mohammed Zuhair Al-Hayali, Choy-Eng Nge, Kuan Hon Lim, Hilary M. Collins, Toh-Seok Kam and Tracey D. Bradshaw
Molecules 2024, 29(11), 2654; https://doi.org/10.3390/molecules29112654 - 4 Jun 2024
Cited by 1 | Viewed by 1241
Abstract
Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine’s broad-spectrum anticancer activity together with that of three [...] Read more.
Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine’s broad-spectrum anticancer activity together with that of three other bisindoles—conophylline, leucophyllidine, and bipleiophylline—against human-derived breast, colorectal, pancreatic, and lung carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (e.g., in MDA-MB-468 breast) or senescence (e.g., in HT-29 colorectal) in cancer cells. Annexin V-FITC/PI, caspase activation, and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Cell cycle perturbations were evident, comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed an induction of aberrant mitotic phenotypes-membrane blebbing, DNA-fragmentation with occasional multi-nucleation. DNA integrity assessment in HCT-116, MDA-MB-468, MIAPaCa-2, and HT-29 cells showed increased fluorescent γ-H2AX during the G1 cell cycle phase; γ-H2AX foci were validated in HCT-116 and MDA-MB-468 cells by confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by increased NQO1 expression. Collectively, we present conofolidine as a putative potent anticancer agent capable of inducing heterogeneous modes of cancerous cell death in vitro, encouraging further preclinical evaluations of this natural product. Full article
(This article belongs to the Special Issue Natural Products Based Anticancer Drugs)
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17 pages, 3246 KiB  
Article
An In Vitro Examination of Whether Kratom Extracts Enhance the Cytotoxicity of Low-Dose Doxorubicin against A549 Human Lung Cancer Cells
by Asep Bayu, Siti Irma Rahmawati, Firmansyah Karim, Jonathan Ardhianto Panggabean, Dasilva Primarindu Nuswantari, Dwi Wahyu Indriani, Peni Ahmadi, Rendi Witular, Ni Luh Putu Indi Dharmayanti and Masteria Yunovilsa Putra
Molecules 2024, 29(6), 1404; https://doi.org/10.3390/molecules29061404 - 21 Mar 2024
Cited by 2 | Viewed by 2963
Abstract
Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement [...] Read more.
Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10–60 ppm of crude and alkaloid extracts derived from the leaves of Kratom (Mitragyna speciosa (Korth.) Havil. Rubiaceae). A549 cancer cell lines were insensitive to the crude extract containing low mitragynine (MG) (4–5%), while these cells were moderately inhibited by the alkaloid extract containing 40–45% MG (IC50 of 48–55 ppm). The alkaloid extract was found to inhibit A549 cancer cells via apoptosis as suggested by the higher relative fluorescence intensity with Annexin compared to that in propidium iodide (PI), i.e., a positive Annexin and a negative PI. The combination of crude extract and doxorubicin sensitized A549 cancer cells to doxorubicin by 1.3 to 2.4 times, while the combination with the alkaloid induced a 2.6- to 3.4-fold increase in sensitivity. The calculated combination index (CI) for doxorubicin with the crude and alkaloid extracts was 0.6 and 0.3, respectively, showing potential synergistic combinations to reduce the level of dosage of doxorubicin used in chemotherapy. In addition, the synergistic enhancement effect of crude extract on the cytotoxic activity of doxorubicin provides insights into the plausibility of non-alkaloids to influence the biological activities of Kratom. Full article
(This article belongs to the Special Issue Natural Products Based Anticancer Drugs)
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22 pages, 5271 KiB  
Article
Shikonin Causes an Apoptotic Effect on Human Kidney Cancer Cells through Ras/MAPK and PI3K/AKT Pathways
by József Király, Erzsébet Szabó, Petra Fodor, Zsolt Fejes, Béla Nagy, Jr., Éva Juhász, Anna Vass, Mahua Choudhury, Gábor Kónya, Gábor Halmos and Zsuzsanna Szabó
Molecules 2023, 28(18), 6725; https://doi.org/10.3390/molecules28186725 - 20 Sep 2023
Cited by 7 | Viewed by 1965
Abstract
(1) Background: Shikonin, the main ingredient in Chinese herbal medicine, is described as a novel angiogenesis inhibitor, and its anticancer effects have already been studied. Shikonin and its derivatives induce apoptosis and suppress metastasis, which further enhance the effectiveness of chemotherapy. However, their [...] Read more.
(1) Background: Shikonin, the main ingredient in Chinese herbal medicine, is described as a novel angiogenesis inhibitor, and its anticancer effects have already been studied. Shikonin and its derivatives induce apoptosis and suppress metastasis, which further enhance the effectiveness of chemotherapy. However, their mechanism of function has not been completely elucidated on human renal cancer cells. (2) Methods: In our study, CAKI-2 and A-498 cells were treated with increasing concentrations (2.5–40 µM) of shikonin, when colony formation ability and cytotoxic activity were tested. The changes in the expression of the main targets of apoptotic pathways were measured by RT-qPCR and Western blot. The intracellular levels of miR-21 and miR-155 were quantified by RT-qPCR. (3) Results: Shikonin exerted a dose-dependent effect on the proliferation of the cell lines examined. In 5 µM concentration of shikonin in vitro elevated caspase-3 and -7 levels, the proteins of the Ras/MAPK and PI3K/AKT pathways were activated. However, no significant changes were detected in the miR-21 and miR-155 expressions. (4) Conclusions: Our findings indicated that shikonin causes apoptosis of renal cancer cells by activating the Ras/MAPK and PI3K/AKT pathways. These effects of shikonin on renal cancer cells may bear important potential therapeutic implications for the treatment of renal cancer. Full article
(This article belongs to the Special Issue Natural Products Based Anticancer Drugs)
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Review

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21 pages, 808 KiB  
Review
New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy
by Aleksandra Majchrzak-Celińska and Elżbieta Studzińska-Sroka
Molecules 2024, 29(7), 1682; https://doi.org/10.3390/molecules29071682 - 8 Apr 2024
Cited by 1 | Viewed by 1523
Abstract
Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their [...] Read more.
Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their poor bioavailability, low tumor accumulation, and rapid clearance compromise their efficacy in vivo. Here, we present the new avenues in phytocompound research for the improvement of glioblastoma therapy, including the ways to enhance the response to temozolomide using phytochemicals, the current focus on phytocompound-based immunotherapy, or the use of phytocompounds as photosensitizers in photodynamic therapy. Moreover, we present new, intensively evaluated approaches, such as chemical modifications of phytochemicals or encapsulation into numerous types of nanoformulations, to improve their bioavailability and delivery to the brain. Finally, we present the clinical trials evaluating the role of phytocompounds or phytocompound-derived drugs in glioblastoma therapy and the less studied phytocompounds or plant extracts that have only recently been found to possess promising anti-glioblastoma properties. Overall, recent advancements in phytocompound research are encouraging; however, only with more 3D glioblastoma models, in vivo studies, and clinical trials it is possible to upgrade the role of phytocompounds in glioblastoma treatment to a satisfactory level. Full article
(This article belongs to the Special Issue Natural Products Based Anticancer Drugs)
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20 pages, 1840 KiB  
Review
The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment
by Zhaowen Liu, Yifan Cao, Xiaohua Guo and Zhixi Chen
Molecules 2023, 28(14), 5500; https://doi.org/10.3390/molecules28145500 - 19 Jul 2023
Cited by 2 | Viewed by 1864
Abstract
Cancer, as one of the leading causes of death worldwide, has challenged current chemotherapy drugs. Considering that treatments are expensive, alongside the resistance of tumor cells to anticancer drugs, the development of alternative medicines is necessary. Anemarrhena asphodeloides Bunge, a recognized and well-known [...] Read more.
Cancer, as one of the leading causes of death worldwide, has challenged current chemotherapy drugs. Considering that treatments are expensive, alongside the resistance of tumor cells to anticancer drugs, the development of alternative medicines is necessary. Anemarrhena asphodeloides Bunge, a recognized and well-known medicinal plant for more than two thousand years, has demonstrated its effectiveness against cancer. Timosaponin-AIII (TSAIII), as a bioactive steroid saponin isolated from A. asphodeloides, has shown multiple pharmacological activities and has been developed as an anticancer agent. However, the molecular mechanisms of TSAIII in protecting against cancer development are still unclear. In this review article, we provide a comprehensive discussion on the anticancer effects of TSAIII, including proliferation inhibition, cell cycle arrest, apoptosis induction, autophagy mediation, migration and invasion suppression, anti-angiogenesis, anti-inflammation, and antioxidant effects. The pharmacokinetic profiles of TSAII are also discussed. TSAIII exhibits efficacy against cancer development. However, hydrophobicity and low bioavailability may limit the application of TSAIII. Effective delivery systems, particularly those with tissue/cell-targeted properties, can also significantly improve the anticancer effects of TSAIII. Full article
(This article belongs to the Special Issue Natural Products Based Anticancer Drugs)
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