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Natural Compounds in Cancer Therapy and Prevention, 2nd Edition
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Natural Compounds in Cancer Therapy and Prevention, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 6993

Special Issue Editors

Dr. Federica Finetti

E-Mail Website
Guest Editor
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, SI, Italy
Interests: antioxidant; anti-inflammatory; antitumoral and antiangiogenic potential of natural compounds; their semisynthetic derivatives and/or analogs produced by metabolic engineering and evaluation of their potential biomedical and nutraceutical applications; molecular mechanisms underlying cerebral cavernous malformation (CCM) with particular focus on the study of physiopathological functions of KRIT1 protein and its functional interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Lorenza Trabalzini

E-Mail Website
Guest Editor
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, SI, Italy
Interests: antioxidant; anti-inflammatory; antitumoral activity; natural compounds; nutraceutical applications; cerebral cavernous malformation; KRIT1
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer prevention and therapy represent the greatest challenges of our time, with major efforts being made to prevent cancer onset and progression and to pharmacologically treat oncologic patients. Currently, naturally derived drugs are used in clinics, such as vincristine, actinomycin D, bleomycin, doxorubicin, irinotecan and many others. However, due to the lack of effective therapeutic strategies for many cancers and the side effects associated with chemotherapy, we must identify new therapeutic approaches. In this context, natural extracts represent a source of new chemicals that could aid the development of new anticancer drugs. Similarly, it is well known that natural extracts may enable cancer prevention, mainly by exerting antioxidant and anti-inflammatory activities. In this context, the identification and the biological characterization of new compounds and the evaluation of their protective and therapeutic effects on cancer progression is of great interest.

The potential topics include, but are not limited to: the anticancer activity of natural compounds; the effects of natural compounds on tumor growth and migration; the antimetastatic activity of natural compounds; natural products in cancer prevention; the isolation and identification of pharmacologically active compounds from natural extracts; drug discovery; and the immunomodulatory activity of natural compounds. In the first volume, 16 papers were published. We invite you to read them publications and contribute to volume 2.0.

Dr. Federica Finetti
Dr. Lorenza Trabalzini
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 therapy

    cancer prevention
  • natural compounds
  • metastasis, immunomodulation
  • adjuvant therapy
  • preventive therapy
  • drug discovery
  • natural drugs

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Related Special Issue

Published Papers (6 papers)

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Research

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21 pages, 20166 KiB  
Article
Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones’ Antimalignancy Properties
by Jakub Rech, Dorota Żelaszczyk, Henryk Marona, Agnieszka Gunia-Krzyżak, Paweł Żmudzki and Ilona Anna Bednarek
Int. J. Mol. Sci. 2024, 25(16), 8874; https://doi.org/10.3390/ijms25168874 - 15 Aug 2024
Viewed by 432
Abstract
In order to improve naturally occurring xanthones’ anticancer properties, chemical synthesis is proposed. In this study, from eight novel xanthone derivatives coupled to morpholine or aminoalkyl morpholine, only the two most active ones were chosen. For additional enhancement of the anticancer activity of [...] Read more.
In order to improve naturally occurring xanthones’ anticancer properties, chemical synthesis is proposed. In this study, from eight novel xanthone derivatives coupled to morpholine or aminoalkyl morpholine, only the two most active ones were chosen. For additional enhancement of the anticancer activity of our tested compounds, we combined chemotherapy with hyperthermia in the range of 39–41 °C, from which the mild conditions of 39 °C were the most influencing. This approach had a profound impact on the anticancer properties of the tested compounds. TOV-21G and SC-OV-3 ovarian cell line motility and metastasis behavior were tested in native and hyperthermia conditions, indicating decreased wound healing properties and clonogenic activity. Similarly, the expression of genes involved in metastasis was hampered. The expression of heat shock proteins involved in cancer progression (Hsc70, HSP90A, and HSP90B) was significantly influenced by xanthone derivatives. Chemotherapy in mild hyperthermia conditions had also an impact on decreasing mitochondria potential, visualized with JC-1. Synthetic xanthone ring modifications may increase the anticancer activity of the obtained substances. Additional improvement of their activity can be achieved by applying mild hyperthermia conditions. Further development of a combined anticancer therapy approach may result in increasing currently known chemotherapeutics, resulting in a greater recovery rate and diminishment of the cytotoxicity of drugs. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention, 2nd Edition)
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22 pages, 9666 KiB  
Article
Anti-Cancer Properties of Two Intravenously Administrable Curcumin Formulations as Evaluated in the 3D Patient-Derived Cancer Spheroid Model
by Marlene Niederreiter, Julia Klein, Sebastian B. M. Schmitz, Jens Werner and Barbara Mayer
Int. J. Mol. Sci. 2024, 25(15), 8543; https://doi.org/10.3390/ijms25158543 - 5 Aug 2024
Viewed by 714
Abstract
Curcumin (Cur) is a heavily used complementary derived drug from cancer patients. Spheroid samples derived from 82 patients were prepared and treated after 48 h with two Cur formulations (CurA, CurB) in mono- and combination therapy. After 72 h, cell viability and morphology [...] Read more.
Curcumin (Cur) is a heavily used complementary derived drug from cancer patients. Spheroid samples derived from 82 patients were prepared and treated after 48 h with two Cur formulations (CurA, CurB) in mono- and combination therapy. After 72 h, cell viability and morphology were assessed. The Cur formulations had significant inhibitory effects of −8.47% (p < 0.001), CurA of −10.01% (−50.14–23.11%, p = 0.001) and CurB of −6.30% (−33.50–19.30%, p = 0.006), compared to their solvent controls Polyethylene-glycol, β-Cyclodextrin (CurA) and Kolliphor-ELP, Citrate (CurB). Cur formulations were more effective in prostate cancer (−19.54%) and less effective in gynecological non-breast cancers (0.30%). CurA showed better responses in samples of patients <40 (−13.81%) and >70 years of age (−17.74%). CurB had stronger effects in metastasized and heavily pretreated tumors. Combinations of Cur formulations and standard therapies were superior in 20/47 samples (42.55%) and inferior in 7/47 (14.89%). CurB stimulated chemo-doublets more strongly than monotherapies (−0.53% vs. −6.51%, p = 0.022) and more effectively than CurA (−6.51% vs. 3.33%, p = 0.005). Combinations of Cur formulations with Artesunate, Resveratrol and vitamin C were superior in 35/70 (50.00%) and inferior in 16/70 (22.86%) of samples. Cur formulations were significantly enhanced by combination with Artesunate (p = 0.020). Cur formulations showed a high variance in their anti-cancer effects, suggesting a need for individual testing before administration. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention, 2nd Edition)
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20 pages, 3550 KiB  
Article
Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments
by Etelka Ferenczi, Péter Keglevich, Bizhar Ahmed Tayeb, Renáta Minorics, Dávid Papp, Gitta Schlosser, István Zupkó, László Hazai and Antal Csámpai
Int. J. Mol. Sci. 2024, 25(13), 7428; https://doi.org/10.3390/ijms25137428 - 6 Jul 2024
Viewed by 796
Abstract
In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, [...] Read more.
In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer), and SH-SY5Y (neuroblastoma) as well as on human embryonal lung fibroblast cell line MRC-5, which served as a reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention, 2nd Edition)
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18 pages, 3877 KiB  
Article
Molecular Aspects of Piperine in Signaling Pathways Associated with Inflammation in Head and Neck Cancer
by Juliana Prado Gusson-Zanetoni, Luana Pereira Cardoso, Stefanie Oliveira de Sousa, Laura Luciana de Melo Moreira Silva, Júlia de Oliveira Martinho, Tiago Henrique, Eloiza Helena Tajara, Sonia Maria Oliani and Flávia Cristina Rodrigues-Lisoni
Int. J. Mol. Sci. 2024, 25(11), 5762; https://doi.org/10.3390/ijms25115762 - 25 May 2024
Viewed by 811
Abstract
Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular [...] Read more.
Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN-γ and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention, 2nd Edition)
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Review

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45 pages, 5649 KiB  
Review
Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads
by Giovanni Tonon, Flavio Rizzolio, Fabiano Visentin and Thomas Scattolin
Int. J. Mol. Sci. 2024, 25(16), 8651; https://doi.org/10.3390/ijms25168651 - 8 Aug 2024
Viewed by 1356
Abstract
This review highlights significant advancements in antibody–drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging [...] Read more.
This review highlights significant advancements in antibody–drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies. Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies. ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention, 2nd Edition)
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58 pages, 1145 KiB  
Review
Natural Compounds for Preventing Age-Related Diseases and Cancers
by Mi-Ran Ki, Sol Youn, Dong Hyun Kim and Seung Pil Pack
Int. J. Mol. Sci. 2024, 25(14), 7530; https://doi.org/10.3390/ijms25147530 - 9 Jul 2024
Viewed by 2409
Abstract
Aging is a multifaceted process influenced by hereditary factors, lifestyle, and environmental elements. As time progresses, the human body experiences degenerative changes in major functions. The external and internal signs of aging manifest in various ways, including skin dryness, wrinkles, musculoskeletal disorders, cardiovascular [...] Read more.
Aging is a multifaceted process influenced by hereditary factors, lifestyle, and environmental elements. As time progresses, the human body experiences degenerative changes in major functions. The external and internal signs of aging manifest in various ways, including skin dryness, wrinkles, musculoskeletal disorders, cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. Additionally, cancer, like aging, is a complex disease that arises from the accumulation of various genetic and epigenetic alterations. Circadian clock dysregulation has recently been identified as an important risk factor for aging and cancer development. Natural compounds and herbal medicines have gained significant attention for their potential in preventing age-related diseases and inhibiting cancer progression. These compounds demonstrate antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic effects as well as circadian clock regulation. This review explores age-related diseases, cancers, and the potential of specific natural compounds in targeting the key features of these conditions. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention, 2nd Edition)
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