1,2-Dihydroxyxanthone: Effect on A375-C5 Melanoma Cell Growth Associated with Interference with THP-1 Human Macrophage Activity

Silva, Viviana; Cerqueira, Fátima; Nazareth, Naïr; Medeiros, Rui; Sarmento, Amélia; Sousa, Emı́lia; Pinto, Madalena

doi:10.3390/ph12020085

Cited by 10 publications

(19 citation statements)

References 79 publications

(108 reference statements)

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“…Treatment with 50 and 100 μM of 14 suppressed the expression of IL-1β and IL-10 by THP-1 macrophages. However, the production of TNF-α was found to increase, suggesting favorability for melanoma treatment based on a previous meta-analysis that linked the development of skin cancers to the use of TNF inhibitors (Mariette et al, 2011;Silva et al, 2019). However, this finding highlighted the contradictions in current literature on the role of TNF-α in skin cancer and melanoma whereby other studies did not support the benefits of upregulating the cytokine (Smith et al, 2014;Mercer et al, 2017).…”

Section: Anti-inflammatory Mechanisms Of Xanthonesmentioning

confidence: 77%

“…Consequently, MAPK cascades as well as the UVB-induced activation and activity of pro-inflammatory transcription factors AP-1 and NF-κB were halted (Li et al, 2012). A recent fascinating study by Silva and colleagues (2019) investigated the modulatory activity of synthetic 1,2-dihydroxyxanthone (14) on THP-1 macrophage activity and A375-C5 melanoma cells (Silva et al, 2019). Treatment with 50 and 100 μM of 14 suppressed the expression of IL-1β and IL-10 by THP-1 macrophages.…”

Section: Anti-inflammatory Mechanisms Of Xanthonesmentioning

confidence: 99%

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Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

et al. 2020

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The pathogenesis of skin inflammatory diseases such as atopic dermatitis, acne, psoriasis, and skin cancers generally involve the generation of oxidative stress and chronic inflammation. Exposure of the skin to external aggressors such as ultraviolet (UV) radiation and xenobiotics induces the generation of reactive oxygen species (ROS) which subsequently activates immune responses and causes immunological aberrations. Hence, antioxidant and anti-inflammatory agents were considered to be potential compounds to treat skin inflammatory diseases. A prime example of such compounds is xanthone (xanthene-9-one), a class of natural compounds that possess a wide range of biological activities including antioxidant, anti-inflammatory, antimicrobial, cytotoxic, and chemotherapeutic effects. Many studies reported various mechanisms of action by xanthones for the treatment of skin inflammatory diseases. These mechanisms of action commonly involve the modulation of various pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α), as well as anti-inflammatory cytokines such as IL-10. Other mechanisms of action include the regulation of NF-κB and MAPK signaling pathways, besides immune cell recruitment via modulation of chemokines, activation, and infiltration. Moreover, disease-specific activity contributed by xanthones, such as antibacterial action against Propionibacterium acnes and Staphylococcus epidermidis for acne treatment, and numerous cytotoxic mechanisms involving pro-apoptotic and anti-metastatic effects for skin cancer treatment have been extensively elucidated. Furthermore, xanthones have been reported to modulate pathways responsible for mediating oxidative stress and inflammation such as PPAR, nuclear factor erythroid 2-related factor and prostaglandin cascades. These pathways were also implicated in skin inflammatory diseases. Xanthones including the prenylated α-mangostin (2) and γ-mangostin (3), glucosylated mangiferin (4) and the caged xanthone gambogic acid (8) are potential lead compounds to be further developed into pharmaceutical agents for the treatment of skin inflammatory diseases. Future studies on the structure-activity relationships, molecular mechanisms, and applications of xanthones for the treatment of skin inflammatory diseases are thus highly recommended.

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Section: Anti-inflammatory Mechanisms Of Xanthonesmentioning

confidence: 77%

Section: Anti-inflammatory Mechanisms Of Xanthonesmentioning

confidence: 99%

Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

et al. 2020

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Section: Introductionmentioning

confidence: 91%

“…This compound can be considered noncytotoxic since an 83% decrease in HaCaT cell viability in the neutral red assay was observed. Additionally, 1,2-DHX (1) did not show any scavenging activity of NO generated in a cell-free system [16,20]. In the light of these recent findings, the optimization of the xanthone structure aiming the discovery of new antioxidants with potential as skin antiaging actives, led us to assemble a small library of polyoxygenated xanthones with privileged patterns of antioxidant motifs such as catechol (1-3), hydroquinone (4), or peri-carbonyl hydroxyl groups (1, 4, and 5; Figure 1) and to investigate their potential for skin care.…”

Section: Introductionmentioning

confidence: 99%

“…In order to further explore the potential of 1,2-DHX ( 1 ), we also investigated its effects on the growth of the A375-C5 melanoma epithelial cell line and its modulatory effects on the activity of the THP-1 macrophage cell line, namely cytokine production. The results suggested a putative impact of 1,2-DHX ( 1 ) in melanoma treatment, not only due to a direct effect on cancer cells but also by modulation of macrophage activity [ 20 ]. Toxicity was excluded by performing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction, neutral red (NR) uptake, Alamar Blue reduction, and Trypan Blue exclusion assays.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging

et al. 2020

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Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (1). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC50 values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl3 and CuCl2) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone (1) was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone (1) was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.

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Synthesis and in vitro assay of hydroxyxanthones as antioxidant and anticancer agents

Fatmasari

Kurniawan

Jumina

et al. 2022

Sci Rep

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In the present work, three hydroxyxanthones were synthesized in 11.15–33.42% yield from 2,6-dihydroxybenzoic acid as the starting material. The chemical structures of prepared hydroxyxanthones have been elucidated by using spectroscopic techniques. Afterward, the hydroxyxanthones were evaluated as antioxidant agents through radical scavenging assay; and anticancer agents through in vitro assays against WiDr, MCF-7, and HeLa cancer cell lines. Hydroxyxanthone 3b was categorized as a strong antioxidant agent (IC50 = 349 ± 68 µM), while the other compounds were categorized as moderate antioxidant agents (IC50 > 500 µM). On the other hand, hydroxyxanthone 3a exhibited the highest anticancer activity (IC50 = 184 ± 15 µM) and the highest selectivity (SI = 18.42) against MCF-7 cancer cells. From the molecular docking study, it was found that hydroxyxanthone 3a interacted with the active sites of Topoisomerase II protein through Hydrogen bonding with DG13 and π–π stacking interactions with DA12 and DC8. These findings revealed that hydroxyxanthones are potential candidates to be developed as antioxidant and anticancer agents in the future.

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1,2-Dihydroxyxanthone: Effect on A375-C5 Melanoma Cell Growth Associated with Interference with THP-1 Human Macrophage Activity

Cited by 10 publications

References 79 publications

Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging

Synthesis and in vitro assay of hydroxyxanthones as antioxidant and anticancer agents

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