Editorial

3 pages, 234 KiB

Open AccessEditorial

Natural Compounds as New Cancer Treatments

by Enrique Barrajón-Catalán

Medicines 2019, 6(3), 78; https://doi.org/10.3390/medicines6030078 - 23 Jul 2019

Cited by 2 | Viewed by 2563

Cancer is still a global challenge worldwide with a high impact not only on human health, causing morbidity and mortality, but also on economics [...] Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

Research

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18 pages, 2033 KiB

Open AccessArticle

Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth

by Tung-chin Chiang, Brian Koss, L. Joseph Su, Charity L. Washam, Stephanie D. Byrum, Aaron Storey and Alan J. Tackett

Medicines 2019, 6(3), 71; https://doi.org/10.3390/medicines6030071 - 27 Jun 2019

Cited by 6 | Viewed by 3644

Abstract

Background: UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2’-deoxycytidine (DAC) [...] Read more.

Background: UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2’-deoxycytidine (DAC) could slow melanoma cell growth. SFN is a natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase inhibitor. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator cytokine—C-C motif ligand 5 (CCL-5)—was validated. Conclusions: These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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11 pages, 574 KiB

Open AccessArticle

Oral Intake of Royal Jelly Has Protective Effects Against Tyrosine Kinase Inhibitor-Induced Toxicity in Patients with Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Trial

by Kyohei Araki, Yasuyoshi Miyata, Kojiro Ohba, Yuichiro Nakamura, Tomohiro Matsuo, Yasushi Mochizuki and Hideki Sakai

Medicines 2019, 6(1), 2; https://doi.org/10.3390/medicines6010002 - 20 Dec 2018

Cited by 15 | Viewed by 5234 | Correction

Abstract

Background: Although tyrosine kinase inhibitors (TKIs) are still recommended as the standard therapy in renal cell carcinoma (RCC), the high frequency of adverse events is a weakness of this therapy. Because royal jelly (RJ) possesses anti-inflammatory and antioxidant properties, we assessed its protective [...] Read more.

Background: Although tyrosine kinase inhibitors (TKIs) are still recommended as the standard therapy in renal cell carcinoma (RCC), the high frequency of adverse events is a weakness of this therapy. Because royal jelly (RJ) possesses anti-inflammatory and antioxidant properties, we assessed its protective effects on TKI-induced toxicities in RCC patients. Methods: We enrolled 33 patients with advanced RCC who were assigned to start TKI therapy in combination with a randomized, double-blinded, placebo-controlled RJ trial consisting of a placebo group with 17 subjects and an RJ group with 16 subjects. Results: Fatigue and anorexia frequencies in the RJ group were significantly lower than in the placebo group (p = 0.003 and 0.015, respectively). A statistically significant correlation between RJ and fatigue or anorexia was detected in sunitinib-treated patients. The dose reduction- or discontinuation-free periods were significantly longer (p = 0.013) in the RJ group than in the placebo group. Furthermore, similar observations were made in sunitinib-treated patients (p = 0.016). Conclusions: Our clinical trial showed that RJ exerted protective effects against TKI-induced fatigue and anorexia and lowered TKI dose reduction or discontinuation. Hence, RJ is beneficial for maintaining the quality of life and medication compliance in TKI-treated RCC patients. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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18 pages, 3065 KiB

Open AccessFeature PaperArticle

Bioactive Composition, Antioxidant Activity, and Anticancer Potential of Freeze-Dried Extracts from Defatted Gac (Momordica cochinchinensis Spreng) Seeds

by Anh V. Le, Tien T. Huynh, Sophie E. Parks, Minh H. Nguyen and Paul D. Roach

Medicines 2018, 5(3), 104; https://doi.org/10.3390/medicines5030104 - 18 Sep 2018

Cited by 12 | Viewed by 4536

Abstract

Background: Gac (Momordica cochinchinensis Spreng) seeds have long been used in traditional medicine as a remedy for numerous conditions due to a range of bioactive compounds. This study investigated the solvent extraction of compounds that could be responsible for antioxidant activity and [...] Read more.

Background: Gac (Momordica cochinchinensis Spreng) seeds have long been used in traditional medicine as a remedy for numerous conditions due to a range of bioactive compounds. This study investigated the solvent extraction of compounds that could be responsible for antioxidant activity and anticancer potential. Methods: Defatted Gac seed kernel powder was extracted with different solvents: 100% water, 50% methanol:water, 70% ethanol:water, water saturated butanol, 100% methanol, and 100% ethanol. Trypsin inhibitors, saponins, phenolics, and antioxidant activity using the 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the ferric reducing antioxidant power (FRAP) assays; and anticancer potential against two melanoma cancer cell lines (MM418C1 and D24) were analysed to determine the best extraction solvents. Results: Water was best for extracting trypsin inhibitors (581.4 ± 18.5 mg trypsin/mg) and reducing the viability of MM418C1 and D24 melanoma cells (75.5 ± 1.3 and 66.9 ± 2.2%, respectively); the anticancer potential against the MM418C1 cells was highly correlated with trypsin inhibitors (r = 0.92, p < 0.05), but there was no correlation between anticancer potential and antioxidant activity. The water saturated butanol had the highest saponins (71.8 ± 4.31 mg aescin equivalents/g), phenolic compounds (20.4 ± 0.86 mg gallic acid equivalents/g), and antioxidant activity, but these measures were not related to anticancer potential. Conclusions: Water yielded a Gac seed extract, rich in trypsin inhibitors, which had high anticancer potential against two melanoma cell lines. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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Review

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12 pages, 685 KiB

Open AccessReview

Differential Methylation and Acetylation as the Epigenetic Basis of Resveratrol’s Anticancer Activity

by Mohd Farhan, Mohammad Fahad Ullah, Mohd Faisal, Ammad Ahmad Farooqi, Uteuliyev Yerzhan Sabitaliyevich, Bernhard Biersack and Aamir Ahmad

Medicines 2019, 6(1), 24; https://doi.org/10.3390/medicines6010024 - 13 Feb 2019

Cited by 24 | Viewed by 4838

Abstract

Numerous studies support the potent anticancer activity of resveratrol and its regulation of key oncogenic signaling pathways. Additionally, the activation of sirtuin 1, a deacetylase, by resveratrol has been known for many years, making resveratrol perhaps one of the earliest nutraceuticals with associated [...] Read more.

Numerous studies support the potent anticancer activity of resveratrol and its regulation of key oncogenic signaling pathways. Additionally, the activation of sirtuin 1, a deacetylase, by resveratrol has been known for many years, making resveratrol perhaps one of the earliest nutraceuticals with associated epigenetic activity. Such epigenetic regulation by resveratrol, and the mechanism thereof, has attracted much attention in the past decade. Focusing on methylation and acetylation, the two classical epigenetic regulations, we showcase the potential of resveratrol as an effective anticancer agent by virtue of its ability to induce differential epigenetic changes. We discuss the de-repression of tumor suppressors such as BRCA-1, nuclear factor erythroid 2-related factor 2 (NRF2) and Ras Associated Domain family-1α (RASSF-1α) by methylation, PAX1 by acetylation and the phosphatase and tensin homologue (PTEN) by both methylation and acetylation, in addition to the epigenetic regulation of oncogenic NF-κB and STAT3 signaling by resveratrol. Further, we evaluate the literature supporting the potentiation of HDAC inhibitors and the inhibition of DNMTs by resveratrol in different human cancers. This discussion underlines a robust epigenetic activity of resveratrol that warrants further evaluation, particularly in clinical settings. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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10 pages, 1287 KiB

Open AccessReview

The Multitarget Activity of Natural Extracts on Cancer: Synergy and Xenohormesis

by María Herranz-López, María Losada-Echeberría and Enrique Barrajón-Catalán

Medicines 2019, 6(1), 6; https://doi.org/10.3390/medicines6010006 - 28 Dec 2018

Cited by 25 | Viewed by 4233

Abstract

It is estimated that over 60% of the approved drugs and new drug developments for cancer and infectious diseases are from natural origin. The use of natural compounds as a potential source of antitumor agents has been deeply studied in many cancer models, [...] Read more.

It is estimated that over 60% of the approved drugs and new drug developments for cancer and infectious diseases are from natural origin. The use of natural compounds as a potential source of antitumor agents has been deeply studied in many cancer models, both in vitro and in vivo. Most of the Western medicine studies are based on the use of highly selective pure compounds with strong specificity for their targets such as colchicine or taxol. Nevertheless, approximately 60% of fairly specific drugs in their initial research fail because of toxicity or ineffectiveness in late-stage preclinical studies. Moreover, cancer is a multifaceted disease that in most cases deserves a polypharmacological therapeutic approach. Complex plant-derived mixtures such as natural extracts are difficult to characterize and hardly exhibit high pharmacological potency. However, in some cases, these may provide an advantage due to their multitargeted mode of action and potential synergistic behavior. The polypharmacology approach appears to be a plausible explanation for the multigargeted mechanism of complex natural extracts on different proteins within the same signalling pathway and in several biochemical pathways at once. This review focuses on the different aspects of natural extracts in the context of anticancer activity drug development, with special attention to synergy studies and xenohormesis. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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14 pages, 735 KiB

Open AccessReview

Probiotics in the Treatment of Colorectal Cancer

by Robert Hendler and Yue Zhang

Medicines 2018, 5(3), 101; https://doi.org/10.3390/medicines5030101 - 07 Sep 2018

Cited by 54 | Viewed by 7057

Abstract

The human microbiome plays many roles in inflammation, drug metabolism, and even the development of cancer that we are only beginning to understand. Colorectal cancer has been a focus for study in this field as its pathogenesis and its response to treatment have [...] Read more.

The human microbiome plays many roles in inflammation, drug metabolism, and even the development of cancer that we are only beginning to understand. Colorectal cancer has been a focus for study in this field as its pathogenesis and its response to treatment have both been linked to the functioning of microbiota. This literature review evaluates the animal and human studies that have explored this relationship. By manipulating the microbiome with interventions such as probiotic administration, we may be able to reduce colorectal cancer risk and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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18 pages, 415 KiB

Open AccessReview

Anticancer Effects of Green Tea and the Underlying Molecular Mechanisms in Bladder Cancer

by Yasuyoshi Miyata, Tomohiro Matsuo, Kyohei Araki, Yuichiro Nakamura, Yuji Sagara, Kojiro Ohba and Hideki Sakai

Medicines 2018, 5(3), 87; https://doi.org/10.3390/medicines5030087 - 10 Aug 2018

Cited by 40 | Viewed by 5462

Abstract

Green tea and green tea polyphenols (GTPs) are reported to inhibit carcinogenesis and malignant behavior in several diseases. Various in vivo and in vitro studies have shown that GTPs suppress the incidence and development of bladder cancer. However, at present, opinions concerning the [...] Read more.

Green tea and green tea polyphenols (GTPs) are reported to inhibit carcinogenesis and malignant behavior in several diseases. Various in vivo and in vitro studies have shown that GTPs suppress the incidence and development of bladder cancer. However, at present, opinions concerning the anticancer effects and preventive role of green tea are conflicting. In addition, the detailed molecular mechanisms underlying the anticancer effects of green tea in bladder cancer remain unclear, as these effects are regulated by several cancer-related factors. A detailed understanding of the pathological roles and regulatory mechanisms at the molecular level is necessary for advancing treatment strategies based on green tea consumption for patients with bladder cancer. In this review, we discuss the anticancer effects of GTPs on the basis of data presented in in vitro studies in bladder cancer cell lines and in vivo studies using animal models, as well as new treatment strategies for patients with bladder cancer, based on green tea consumption. Finally, on the basis of the accumulated data and the main findings, we discuss the potential usefulness of green tea as an antibladder cancer agent and the future direction of green tea-based treatment strategies for these patients. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

13 pages, 315 KiB

Open AccessReview

MiR-663, a MicroRNA Linked with Inflammation and Cancer That Is under the Influence of Resveratrol

by Jean-Jacques Michaille, Victoria Piurowski, Brooke Rigot, Hesham Kelani, Emily C. Fortman and Esmerina Tili

Medicines 2018, 5(3), 74; https://doi.org/10.3390/medicines5030074 - 09 Jul 2018

Cited by 14 | Viewed by 3507

Abstract

Resveratrol (trans-3,5,4′-trihydroxystilbene, RSV) is a non-flavonoid dietary polyphenol with antioxidant, anti-inflammatory and anti-cancer properties that is primarily found in red berries. While RSV displays many beneficial effects in vitro, its actual effects in vivo or in animal models remain passionately debated. Recent publications [...] Read more.

Resveratrol (trans-3,5,4′-trihydroxystilbene, RSV) is a non-flavonoid dietary polyphenol with antioxidant, anti-inflammatory and anti-cancer properties that is primarily found in red berries. While RSV displays many beneficial effects in vitro, its actual effects in vivo or in animal models remain passionately debated. Recent publications suggest that RSV pleiotropic effects could arise from its capability to regulate the expression and activity of microRNAs, short regulators themselves capable of regulating up to several hundreds of target genes. In particular, RSV increases microRNA miR-663 expression in different human cell lines, suggesting that at least some of its multiple beneficial properties are through the modulation of expression of this microRNA. Indeed, the expression of microRNA miR-663 is reduced in certain cancers where miR-663 is considered to act as a tumor suppressor gene, as well as in other pathologies such as cardiovascular disorders. Target of miR-663 include genes involved in tumor initiation and/or progression as well as genes involved in pathologies associated with chronic inflammation. Here, we review the direct and indirect effects of RSV on the expression of miR-663 and its target transcripts, with emphasise on TGFβ1, and their expected health benefits, and argue that elucidating the molecular effects of different classes of natural compounds on the expression of microRNAs should help to identify new therapeutic targets and design new treatments. Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

Other

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2 pages, 201 KiB

Open AccessCorrection

Correction: Oral Intake of Royal Jelly Has Protective Effects against Tyrosine Kinase Inhibitor-Induced Toxicity in Patients with Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Trial. Medicines, 2019, 6, 2

by Kyohei Araki, Yasuyoshi Miyata, Kojiro Ohba, Yuichiro Nakamura, Tomohiro Matsuo, Yasushi Mochizuki and Hideki Sakai

Medicines 2020, 7(11), 71; https://doi.org/10.3390/medicines7110071 - 19 Nov 2020

Cited by 2 | Viewed by 2774

Abstract

We, the authors, wish to make the following correction to our published paper [...] Full article

(This article belongs to the Special Issue Natural Compounds as New Cancer Treatments)

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