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Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 μM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.
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http://dx.doi.org/10.3390/ijms22094870 | DOI Listing |
J Biomol Struct Dyn
December 2024
Department of Science and Technology, Virology and Vaccine Research Program, Industrial Technology Development Institute, Taguig City, Philippines.
The Nipah virus (NiV), a highly pathogenic zoonotic virus of the family, poses significant threats with its alarming mortality rates and pandemic potential. Despite historical cases, effective therapeutics remain elusive, prompting urgent exploration of potential antivirals. In this study, a structure-based virtual screening approach was employed to evaluate 690 metabolites sourced from ten medicinal plants () for their antiviral activity against Nipah virus proteins.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2024
School of Marxism, Shaanxi University of Chinese Medicine, Xi'an, China.
Mugua is a Chinese herbal medicine derived from the dried mature fruit of Chaenomeles speciosa (Sweet) Nakai. This study aimed to dissect the active ingredients and mechanism of Mugua. In the present study, the active components of Mugua were collected and screened through databases combined with UPLC-Q/TOF-MS based qualitative analysis and literature mining, and their potential disease targets were predicted.
View Article and Find Full Text PDFBioorg Chem
December 2024
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China. Electronic address:
The inhibition of HBV DNA and elimination of HBsAg has already been established as an indicator for HBV clinic cure, and a novel dual-targeting inhibitors of HBV polymerase/entry are designed and synthesized in this study. Pentacyclic triterpenes (PTs) scaffold of exhibiting a high affinity to NTCP, including glycyrrhitinic acid (GA), oleanolic acid (OA), ursolic acid (UA), and betulinic acid (BA) were linked neatly with the nucleoside drug zidovudine (AZT) through a molecular hybrid strategy to synthesize twenty of PTs-AZT conjugates for targeting HBV polymerase as well as sodium taurocholate cotransporting polypeptide (NTCP). The conjugates showed significant inhibitory effects on the secretion of HBsAg and HBeAg in HepG2.
View Article and Find Full Text PDFMicrob Biotechnol
December 2024
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Queensland, Australia.
Plant-derived triterpenoids are in high demand due to their valuable applications in cosmetic, nutraceutical, and pharmaceutical industries. To meet this demand, microbial production of triterpenoids is being developed for large-scale production. However, a prominent limitation of microbial synthesis is the intracellular accumulation, requiring cell disruption during downstream processing.
View Article and Find Full Text PDFPentacyclic triterpenoids, as important representatives of natural products, have garnered widespread attention due to their diverse biological activities, including anti-inflammatory, antiviral, and antitumor effects. Oleanolic acid (OA), betulinic acid (BA), ursolic acid (UA), triptolide, and glycyrrhetinic acid (GA) are typical examples of pentacyclic triterpenoids. Despite their significant biological activities, their poor water solubility and low bioavailability have limited further development and application.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!