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Natural Bioactives on Cellular Mechanisms: Cell-Survival and Apoptosis

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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: closed (30 June 2021) | Viewed by 19654

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Special Issue Editor

Dr. Amélia M. Silva

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Guest Editor

1. Department of Biology and Environment, School of Life Sciences and Environment ; Universidade de Trás-os-Montes e Alto Douro (UTAD), 5001-801 Vila Real, Portugal
2. Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB-UTAD), 5001-801 Vila Real, Portugal
Interests: cell biology and biochemistry; cell-based assays; evaluation of bioactivities of natural compounds; phytochemicals; nutraceuticals; nanoencapsulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural bioactives, such as polyphenols, terpenes, and alkaloids, have been described as modulators of several biochemical pathways involved in cell survival and apoptosis. These molecules may have a relevant role modulating cell proliferation, by regulating specific targets, acting as anticancer natural drugs, or favoring cell repair. The boundary between what are the bioactive molecules with an anticancer potential and toxicity is very weak; hence, there is a need to identify the molecular targets of natural bioactives, aiming to validate their potential effect. This Special Issue aims to cover a selection of research papers and reviews that expands and deepens the knowledge regarding the cellular molecular targets of natural bioactives described as having an anticancer activity. Therefore, we sincerely welcome studies reporting the action of natural compounds as novel anticancer agents, emphasizing the mechanisms of action, the molecular targets, active substance verification in vivo and in vitro, and new experimental approaches to enhance their efficacy.

Prof. Dr. Amélia M. Silva
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.

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Keywords

natural bioactives
apoptosis
cell-survival
cell-cycle arrest
oxidative stress
anti-proliferative

Published Papers (5 papers)

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Research

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20 pages, 2597 KiB

Open AccessArticle

Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines

by Marinela Bostan, Mirela Mihaila, Georgiana Gabriela Petrica-Matei, Nicoleta Radu, Razvan Hainarosie, Cristian Dragos Stefanescu, Viviana Roman and Carmen Cristina Diaconu

Int. J. Mol. Sci. 2021, 22(12), 6322; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126322 - 12 Jun 2021

Cited by 15 | Viewed by 2681

Abstract

In head and neck cancers, the effectiveness of cisplatin (CisPt) treatment is limited by its toxicity, especially when higher doses are necessary, and the possible occurrence of cisplatin resistance. This study evaluated the effects of resveratrol (RSV) on the expression of different genes involved in the response of human tumor cells (FaDu, PE/CA-PJ49) to cisplatin therapy. Our results revealed that RSV induced apoptosis amplification in both FaDu and PE/CA-PJ49 cells and modulated the expression of specific genes differently than in normal HaCaT cells. In FaDu cells, combined CisPt + RSV treatment induced an increase in apoptosis, which was associated with an increase in c-MYC and TP53 and a decrease in BCL-2 expression. While CisPt + RSV treatment induced apoptosis in PE/CA-PJ49 cells by inhibition of BCL-2 associated with high levels of MDM-2 and subsequently led to inhibition of TP53 gene expression. Decreased c-MYC expression in PE/CA-PJ49 treated with CisPt + RSV was accompanied by cell cycle blockage in G0/G1 phase. In conclusion, RSV influences tumor cell response to CisPt by inducing apoptosis and modulating gene expression. In addition, in normal HaCaT cells, RSV was able to reduce the harmful effects of CisPt. Full article

(This article belongs to the Special Issue Natural Bioactives on Cellular Mechanisms: Cell-Survival and Apoptosis)

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16 pages, 3671 KiB

Open AccessArticle

Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca²⁺ Overload in Retinal Pigment Epithelial Cells Independently of ROS

by Da Hye Kim, Jeong-Hwan Kim, Hyun Hwangbo, So Young Kim, Seon Yeong Ji, Min Yeong Kim, Hee-Jae Cha, Cheol Park, Su Hyun Hong, Gi-Young Kim, Seh-Kwang Park, Ji-Won Jeong, Mi-Young Kim, Yung Hyun Choi and Hyesook Lee

Int. J. Mol. Sci. 2021, 22(3), 1361; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031361 - 29 Jan 2021

Cited by 16 | Viewed by 3419

Abstract

Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H₂O₂)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H₂O₂ increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H₂O₂-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H₂O₂ insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca²⁺ levels resulting from endoplasmic reticulum stress in H₂O₂-stimulated human RPE cells. Treatment with a cytosolic Ca²⁺ chelator markedly reversed H₂O₂-induced cellular dysfunction. Overall, spermidine protected against H₂O₂-induced cellular damage by blocking the increase of intracellular Ca²⁺ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases. Full article

(This article belongs to the Special Issue Natural Bioactives on Cellular Mechanisms: Cell-Survival and Apoptosis)

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15 pages, 1139 KiB

Open AccessArticle

Enhanced Yield of Bioactivities from Onion (Allium cepa L.) Skin and Their Antioxidant and Anti-α-Amylase Activities

by Mariana Gois Ruivo da Silva, Mihaela Skrt, Draženka Komes, Nataša Poklar Ulrih and Lea Pogačnik

Int. J. Mol. Sci. 2020, 21(8), 2909; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082909 - 21 Apr 2020

Cited by 19 | Viewed by 4349

Abstract

There is increasing concern for reduction of the ecological impacts of industrial waste caused by fruits and vegetables. To reduce costs of onion waste disposal while obtaining value-added products, onion skin can be used to extract quercetin, a natural flavonoid with antioxidant, anti-inflammatory and anti-cancer effects. The aim was to optimize quercetin extraction from brown onion (Allium cepa L.) skin through investigation of the effects of different parameters on quercetin yield. Operational parameters for conventional maceration extraction and for ultrasound-assisted extraction were compared: solvent type, mass-to-liquid ratio, extraction time and temperature. Antioxidant capacity was determined using DPPH· radical scavenging assays and quercetin yield using HPLC/DAD. Anti-α-amylase activity of onion skin extracts was investigated using α-amylase inhibition assays. Optimal extraction conditions of quercetin from onion skin were obtained with maceration extraction, 50% ethanol, 1:100 mass-to-liquid ratio, 25 °C, for 15 min. Under these conditions, the antioxidant capacity (expressed as quercetin equivalents) was 18.7 mg/g and the mass fraction of quercetin was 7.96 mg/g. The onion skin extracts showed a dose-dependent relationship between dry extract concentration and α-amylase inhibition, which confirms that this onion skin extract can be considered as an anti-diabetes agent. Full article

(This article belongs to the Special Issue Natural Bioactives on Cellular Mechanisms: Cell-Survival and Apoptosis)

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Review

Jump to: Research

32 pages, 2279 KiB

Open AccessReview

Natural Compounds as Promising Adjuvant Agents in The Treatment of Gliomas

by Francesca Persano, Giuseppe Gigli and Stefano Leporatti

Int. J. Mol. Sci. 2022, 23(6), 3360; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063360 - 20 Mar 2022

Cited by 18 | Viewed by 3804

Abstract

In humans, glioblastoma is the most prevalent primary malignant brain tumor. Usually, glioblastoma has specific characteristics, such as aggressive cell proliferation and rapid invasion of surrounding brain tissue, leading to a poor patient prognosis. The current therapy—which provides a multidisciplinary approach with surgery followed by radiotherapy and chemotherapy with temozolomide—is not very efficient since it faces clinical challenges such as tumor heterogeneity, invasiveness, and chemoresistance. In this respect, natural substances in the diet, integral components in the lifestyle medicine approach, can be seen as potential chemotherapeutics. There are several epidemiological studies that have shown the chemopreventive role of natural dietary compounds in cancer progression and development. These heterogeneous compounds can produce anti-glioblastoma effects through upregulation of apoptosis and autophagy; allowing the promotion of cell cycle arrest; interfering with tumor metabolism; and permitting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis inhibition. Although these beneficial effects are promising, the efficacy of natural compounds in glioblastoma is limited due to their bioavailability and blood–brain barrier permeability. Thereby, further clinical trials are necessary to confirm the in vitro and in vivo anticancer properties of natural compounds. In this article, we overview the role of several natural substances in the treatment of glioblastoma by considering the challenges to be overcome and future prospects. Full article

(This article belongs to the Special Issue Natural Bioactives on Cellular Mechanisms: Cell-Survival and Apoptosis)

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36 pages, 1142 KiB

Open AccessReview

Chemopreventive Effect of Dietary Anthocyanins against Gastrointestinal Cancers: A Review of Recent Advances and Perspectives

by K.V. Surangi Dharmawansa, David W. Hoskin and H. P. Vasantha Rupasinghe

Int. J. Mol. Sci. 2020, 21(18), 6555; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186555 - 08 Sep 2020

Cited by 29 | Viewed by 4461

Abstract

Anthocyanins are a group of dietary polyphenols, abundant mainly in fruits and their products. Dietary interventions of anthocyanins are being studied extensively related to the prevention of gastrointestinal (GI) cancer, among many other chronic disorders. This review summarizes the hereditary and non-hereditary characteristics of GI cancers, chemistry, and bioavailability of anthocyanins, and the most recent findings of anthocyanin in GI cancer prevention through modulating cellular signaling pathways. GI cancer-preventive attributes of anthocyanins are primarily due to their antioxidative, anti-inflammatory, and anti-proliferative properties, and their ability to regulate gene expression and metabolic pathways, as well as induce the apoptosis of cancer cells. Full article

(This article belongs to the Special Issue Natural Bioactives on Cellular Mechanisms: Cell-Survival and Apoptosis)

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