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Anticancer Activity of Natural Products and Related Compounds
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Anticancer Activity of Natural Products and Related Compounds

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

Deadline for manuscript submissions: 20 September 2024 | Viewed by 3738

Special Issue Editor

Dr. Srinivasa Reddy Bonam

E-Mail Website
Guest Editor
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Interests: natural products and drug discovery; development of novel vaccine adjuvants (DENOVA); anticancer agents; autophagy; regulatory T cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor is a widespread global disease with an extremely high mortality rate. Malignant tumors (cancer) have become one of the major diseases that seriously threaten the physical and mental health of people around the world, and the number of cases is increasing year by year. Thus, there is an urgent need to develop new anti-cancer drugs to selectively inhibit cancer cells, limit their chemoresistance and recurrence after treatment, and establish secondary cancer treatment options.

Carcinogenesis is a complex multistage process in which normal cells are transformed through changes in DNA structure/function into malignant cells with diverse properties, such as abnormal proliferation and reduced apoptosis. Research shows that natural products are one of the important sources of anti-tumor drugs. Many bioactive compounds from different natural sources in vitro and in vivo can affect the several pathways related to tumor development. Therefore, natural products are important and valuable resources for identifying and developing new cancer treatments.

This Special Issue will focus on the anti-tumor activity of functional molecular substances derived from natural products against all types of tumor diseases. Topics include isolation and structure elucidation, phytochemistry, synthesis, medicinal chemistry, pharmacology, chemical biology, molecular biology, mechanism of action of natural products, etc.

Dr. Srinivasa Reddy Bonam
Guest Editor

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

  • anticancer agent
  • natural product chemistry
  • isolation and structure elucidation
  • medicinal chemistry
  • molecular mechanism
  • targeted therapy
  • structure–activity relationships
  • phytochemistry
  • chemical biology

Published Papers (3 papers)

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Research

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13 pages, 2341 KiB  
Article
Carnosic Acid against Lung Cancer: Induction of Autophagy and Activation of Sestrin-2/LKB1/AMPK Signalling
by Eric J. O’Neill, Newman Siu Kwan Sze, Rebecca E. K. MacPherson and Evangelia Tsiani
Int. J. Mol. Sci. 2024, 25(4), 1950; https://doi.org/10.3390/ijms25041950 - 06 Feb 2024
Viewed by 984
Abstract
Non-small cell lung cancer (NSCLC) represents 80% of all lung cancer cases and is characterized by low survival rates due to chemotherapy and radiation resistance. Novel treatment strategies for NSCLC are urgently needed. Liver kinase B1 (LKB1), a tumor suppressor prevalently mutated in [...] Read more.
Non-small cell lung cancer (NSCLC) represents 80% of all lung cancer cases and is characterized by low survival rates due to chemotherapy and radiation resistance. Novel treatment strategies for NSCLC are urgently needed. Liver kinase B1 (LKB1), a tumor suppressor prevalently mutated in NSCLC, activates AMP-activated protein kinase (AMPK) which in turn inhibits mammalian target of rapamycin complex 1 (mTORC1) and activates unc-51 like autophagy activating kinase 1 (ULK1) to promote autophagy. Sestrin-2 is a stress-induced protein that enhances LKB1-dependent activation of AMPK, functioning as a tumor suppressor in NSCLC. In previous studies, rosemary (Rosmarinus officinalis) extract (RE) activated the AMPK pathway while inhibiting mTORC1 to suppress proliferation, survival, and migration, leading to the apoptosis of NSCLC cells. In the present study, we investigated the anticancer potential of carnosic acid (CA), a bioactive polyphenolic diterpene compound found in RE. The treatment of H1299 and H460 NSCLC cells with CA resulted in concentration and time-dependent inhibition of cell proliferation assessed with crystal violet staining and 3H-thymidine incorporation, and concentration-dependent inhibition of survival, assessed using a colony formation assay. Additionally, CA induced apoptosis of H1299 cells as indicated by decreased B-cell lymphoma 2 (Bcl-2) levels, increased cleaved caspase-3, -7, poly (ADP-ribose) polymerase (PARP), Bcl-2-associated X protein (BAX) levels, and increased nuclear condensation. These antiproliferative and proapoptotic effects coincided with the upregulation of sestrin-2 and the phosphorylation/activation of LKB1 and AMPK. Downstream of AMPK signaling, CA increased levels of autophagy marker light chain 3 (LC3), an established marker of autophagy; inhibiting autophagy with 3-methyladenine (3MA) blocked the antiproliferative effect of CA. Overall, these data indicate that CA can inhibit NSCLC cell viability and that the underlying mechanism of action of CA involves the induction of autophagy through a Sestrin-2/LKB1/AMPK signaling cascade. Future experiments will use siRNA and small molecule inhibitors to better elucidate the role of these signaling molecules in the mechanism of action of CA as well as tumor xenograft models to assess the anticancer properties of CA in vivo. Full article
(This article belongs to the Special Issue Anticancer Activity of Natural Products and Related Compounds)
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14 pages, 1686 KiB  
Article
Design, Synthesis and Gene Modulation Insights into Pigments Derived from Tryptophan-Betaxanthin, Which Act against Tumor Development in Caenorhabditis elegans
by Paula Henarejos-Escudero, Fernando F. Méndez-García, Samanta Hernández-García, Pedro Martínez-Rodríguez and Fernando Gandía-Herrero
Int. J. Mol. Sci. 2024, 25(1), 63; https://doi.org/10.3390/ijms25010063 - 20 Dec 2023
Viewed by 780
Abstract
The use of betalains, which are nitrogenous plant pigments, by the food industry is widespread and reflects their safety after intake. The recent research showed outstanding results for L-tryptophan-betaxanthin, a phytochemical present in traditional Chinese medicine, as an antitumoral agent when the activity [...] Read more.
The use of betalains, which are nitrogenous plant pigments, by the food industry is widespread and reflects their safety after intake. The recent research showed outstanding results for L-tryptophan-betaxanthin, a phytochemical present in traditional Chinese medicine, as an antitumoral agent when the activity was evaluated in the animal model Caenorhabditis elegans. Thus, L-tryptophan-betaxanthin is now presented as a lead compound, from which eleven novel structurally related betaxanthins have been designed, biotechnologically produced, purified, and characterized. The antitumoral effect of the derived compounds was evaluated on the JK1466 tumoral strain of C. elegans. All the tested molecules significantly reduced the tumoral gonad sizes in a range between 31.4% and 43.0%. Among the novel compounds synthesized, tryptophan methyl ester-betaxanthin and tryptophan benzyl ester-betaxanthin, which are the first betalains to contain an ester group in their structures, caused tumor size reductions of 43.0% and 42.6%, respectively, after administration to the model animal. Since these were the two most effective molecules, their mechanism of action was investigated by microarray analysis. Differential gene expression analysis showed that tryptophan methyl ester-betaxanthin and tryptophan benzyl ester-betaxanthin were able to down-regulate the key genes of the mTOR pathway, such as daf-15 and rict-1. Full article
(This article belongs to the Special Issue Anticancer Activity of Natural Products and Related Compounds)
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Review

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14 pages, 1010 KiB  
Review
Quercetin Derivatives as Potential Therapeutic Agents: An Updated Perspective on the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer
by Naser A. Alsharairi
Int. J. Mol. Sci. 2023, 24(20), 15208; https://doi.org/10.3390/ijms242015208 - 15 Oct 2023
Cited by 2 | Viewed by 1561
Abstract
Flavonoids are the largest group of polyphenols, represented by many compounds that exhibit high anticancer properties. Quercetin (Q) and its main derivatives (rutin, quercitrin, isoquercitrin, isorhamnetin, tamarixetin, rhamnetin, and hyperoside) in the class of flavonols have been documented to exert anticancer activity. Q [...] Read more.
Flavonoids are the largest group of polyphenols, represented by many compounds that exhibit high anticancer properties. Quercetin (Q) and its main derivatives (rutin, quercitrin, isoquercitrin, isorhamnetin, tamarixetin, rhamnetin, and hyperoside) in the class of flavonols have been documented to exert anticancer activity. Q has been shown to be useful in the treatment of non-small cell lung cancer (NSCLC), as demonstrated by in vitro/in vivo studies, due to its antitumor, anti-inflammatory, anti-proliferative, anti-angiogenesis, and apoptotic properties. Some flavonoids (flavone, anthocyanins, and proanthocyanidins) have been demonstrated to be effective in nicotine-induced NSCLC treatment. However, the molecular mechanisms of quercetin derivatives (QDs) in nicotine-induced NSCLC treatment remain unclear. Thus, this review aims to summarize the available literature on the therapeutic effects of QDs in nicotine-induced NSCLC. Full article
(This article belongs to the Special Issue Anticancer Activity of Natural Products and Related Compounds)
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