Maslinic acid induces autophagy and ferroptosis via transcriptomic and metabolomic reprogramming in prostate cancer cells

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 18, 2024

Prostate cancer has the second highest incidence among male malignancies. Only a few studies exist on inhibitory effects of maslinic acid (MA) prostate cancer. Herein we found that MA inhibits cell proliferation by decreasing CDK2, CDK4, and CDK6 expression concurrently increasing p27, Rb, p-Rb expression. Further, was observed to induce autophagy p53, p-p53, ULK1, Beclin1, Atg7, Atg5 ratio LC3-II/I ERK1/2 mTOR. In addition, induced RM-1 ferroptosis regulating glutathione, glutamate, oxidized glutathione concentrations, inhibiting SLC7A11 activity, downregulating GPX4 Integrated metabolome transcriptome analysis led identification key pathways (e.g., in metabolism). Real-time quantitative PCR confirmed regulates ABCA1 , JUN NFKBIA . vivo demonstrated 50 mg/kg significantly inhibited growth tumors established using cells. To summarize, report both vitro inducing via transcriptomic metabolomic reprogramming.

Язык: Английский

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Secreted Phospholipases A2: Drivers of Inflammation and Cancer

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12408 - 12408

Опубликована: Ноя. 19, 2024

Secreted phospholipase 2 (sPLA2) is the largest family of A2 (PLA2) enzymes with 11 mammalian isoforms. Each sPLA2 exhibits different localizations and specific properties, being involved in a very wide spectrum biological processes. The enzymatic activity has been well described; however, recent findings have shown that they could regulate signaling pathways by acting directly as ligands. Arachidonic acid (AA) its derivatives are produced collaboration other molecules extracellular space, making important impacts on cellular environment, especially relevant contexts immunity cancer. For these reasons, this review focuses functions processes such promotion EMT, angiogenesis, immunomodulation context tumor initiation progression. Finally, we will also describe how knowledge applied search for new inhibitory compounds can be used cancer treatment.

Язык: Английский

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Synthesis and cytotoxic evaluation of F16 derivatives pentacyclic triterpenoid acids possessing a polyhydroxylated ring A

Research Square (Research Square), Год журнала: 2022, Номер unknown

Опубликована: Июль 21, 2022

Abstract Pentacyclic triterpenoid acids bearing a polyhydroxylated A ring have been found in many plants and are of interest for their biological properties, including antitumor activity. The present article reports on the design synthesis series conjugates cationic mitochondria-targeted compound, 4-(1-H-indol-3-ylvinyl)-N-methylpyridinium iodide (F16), with maslinic, corosolic, asiatic tri-hydroxylated analogue betulinic acid. In new hybrid compounds, triterpenoids were linked to fragment F16 C-28 side chain through butyl spacer. results vitro bioscreening two human tumor cell lines (H1299 A549) noncancer fibroblasts (MEFs) revealed that all studied demonstrated significantly stronger effect than original natural acids. particular, activity corosolic acid conjugate against A549 H1299 was 36 24 times higher ursolic Conjugates oxygenated containing hydroxyl or acetyl groups at C-2 atom C-1/C-2 atoms triterpene core exhibited slight decrease compared corresponding F16-derivatives betulinic, oleanolic Among acceptable selectivity relation non-malignant shown only by derivatives maslinic acids, since they not active agents MEFs within assay.

Язык: Английский

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A Malaprade cleavage, a McMurry ring closure and an intramolecular aldol contraction of maslinic acid’s ring A

Results in Chemistry, Год журнала: 2022, Номер 4, С. 100547 - 100547

Опубликована: Янв. 1, 2022

A silica gel supported Malaprade cleavage of methyl maslinoate (→ 3) followed by a titanium-on-graphite McMurry coupling was established to access 2,12-terpenoid. The microwaves aldol reaction dialdehyde 3 gave ring contracted 5. While parent maslinic acid is minor cytotoxicity, improved cytotoxicity observed in SRB assays for while compound 5 most cytotoxic MCF-7 breast adenocarcinoma cells holding low EC50 = 3.1 μM.

Язык: Английский

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A computational and laboratory approach for the investigation of interactions of peptide conjugated natural terpenes with EpHA2 receptor

Journal of Molecular Modeling, Год журнала: 2023, Номер 29(7)

Опубликована: Июнь 8, 2023

Язык: Английский

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