Comparative Evaluation of Anticancer Activity of Natural Methoxylated Flavones Xanthomicrol and Eupatilin in A375 Skin Melanoma Cells

Abstract

Melanoma is a skin cancer caused by the malignant transformation of melanocytes and cutaneous melanoma represents the most aggressive and deadliest type of skin cancer with an increasing incidence worldwide. The main purpose of the present research was to evaluate the anticancer effects of the natural bioactive compounds xanthomicrol (XAN) and eupatilin (EUP) in human A375 malignant skin melanoma cells, a cell line widely used as an in vitro model of cutaneous melanoma. XAN and EUP are lipophilic methoxylated flavones with antioxidant, anti-inflammatory, and antitumor properties. The effects of XAN and EUP on cell viability, morphology, lipid profile, oxidative status, apoptosis, and mitochondrial membrane polarization were determined and compared in A375 cells. At 24 h-incubation (MTT assay), XAN significantly reduced viability at the dose range of 2.5–200 μM, while EUP showed a significant cytotoxicity from 25 μM. Moreover, both methoxylated flavones induced (at 10 and 25 μM, 24 h-incubation) marked cell morphological alterations (presence of rounded and multi-nucleated cells), signs of apoptosis (NucView 488 assay), and a noteworthy mitochondrial membrane depolarization (MitoView 633 assay), coupled to a marked lipid profile modulation, including variations in the ratio of phospholipid/cholesterol and a decrease in the oleic, palmitic, and palmitoleic acid amounts. Moreover, a remarkable time-dependent ROS generation (2′,7′-dichlorodihydrofluorescein diacetate assay) was observed during 3 h-incubation of A375 cancer cells in the presence of XAN and EUP (10 and 25 μM). Our results confirm the potential antitumor effect of natural EUP and XAN in cutaneous melanoma by the activation of multiple anticancer mechanisms.

Elucidation of Anti-Obesity Mechanisms of Phenolics in Artemisiae argyi Folium (Aiye) by Integrating LC-MS, Network Pharmacology, and Molecular Docking

“…The canonical SMILES of each identified component were input into the inquiry box of both the STP (retrieved from http://www.swisstargetprediction.ch/, accessed on 5 March 2024) [26] and the SEA database (retrieved from https://sea.bkslab.org/, accessed on 5 March 2024) [70]. Homo sapiens was selected as the species for target prediction.…”

“…Pharmacological research has shown that it has anti-virus, anti-bacteria, anti-oxidative, anti-inflammatory, anti-dermatitis, gastro-protective, and anti-cancer effects, mainly due to the presence of essential oils, flavonoids, and organic acids [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Pharmacological research has identified various anti-cancer components of Aiye, including jaceosidin, irigenin, luteolin, eriodictyol, apigenin, eupatilin, casticin, and artemetin [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. In obesity, the secretion of adipokines by adipose tissue was dysregulated, characterized by the up-regulation of proinflammation adipokines and the down-regulation of anti-inflammation adipokines [ 30 ].…”

“…CapillarisinKaempferol 124Anti-oxidation, anti-inflammation, exercise performance improvement, physical fatigue alleviation[41][42][43] Hispidulin120 Anti-inflammation, anti-microbial effects [44-46,99] Capillarisin 114 Anti-asthmatic activity, neuro-protection effects [100,101] Jaceosidin 125 Anti-inflammation and hepatic fibrosis modulation, anti-tumor [19-21,47] Centaureidin 118 Immunomodulatory effects, vasorelaxant activity [102,103] Irigenin 107 Lung injury amelioration, anti-inflammation, anti-cancer effects [48,104] Irigenin 107 Lung injury amelioration, anti-inflammation, anti-cancer effects [48,104]107 Lung injury amelioration, anti-inflammation, anti-cancer effects [48,104] Cirsimaritin Life 2024, 14, x FOR PEER REVIEW 12 of 26 Cirsimaritin 115 Colitis alleviation, anti-diabetic activities, antiinflammation, anti-oxidation, and hepatoprotection effects [49-51] Eupatilin 120 Anti-tumor effects, anti-osteoporosis, gastrointestinal hemorrhage prevention, hyperuricemia attenuation, nephroprotection [26,105-107] 3.6. Construction of PPI Network 115 Colitis alleviation, anti-diabetic activities, anti-inflammation, anti-oxidation, and hepatoprotection effects [49-51] Eupatilin Life 2024, 14, x FOR PEER REVIEW 12 of 26 Cirsimaritin 115 Colitis alleviation, anti-diabetic activities, antiinflammation, anti-oxidation, and hepatoprotection effects [49-51] Eupatilin 120Anti-tumor effects, anti-osteoporosis, gastrointestinal hemorrhage prevention, hyperuricemia attenuation, nephroprotection[26,[105][106][107] …”