Comparative Evaluation of Cytotoxic and Apoptotic Effects of Natural Compounds in SH-SY5Y Neuroblastoma Cells in Relation to Their Physicochemical Properties

• Published in: Molecules (Basel, Switzerland) Vol. 30; no. 8; p. 1742
• Main Authors: Rosa, Antonella, Pollastro, Federica, Sogos, Valeria, Piras, Franca
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.04.2025; MDPI
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidants; Apoptosis; Apoptosis - drug effects; arzanol; Biological Products - chemistry; Biological Products - pharmacology; Cancer therapies; Cell cycle; Cell growth; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Comparative analysis; Cytotoxicity; Drug dosages; Enzymes; eupatilin; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Fluorescence; Humans; Lipids; Natural products; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - metabolism; Neuroblastoma - pathology; Permeability; Pharmacokinetics; Physicochemical properties; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; SH-SY5Y neuroblastoma; Toxicity; Vincristine; xanthomicrol; zerumbone; Italy; SH-SY5Y neuroblastoma; eupatilin; apoptosis; arzanol; xanthomicrol; zerumbone; cytotoxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules30081742

The cytotoxic and apoptotic properties of four bioactive natural compounds, the prenylated α-pyronephloroglucinol heterodimer arzanol (ARZ), the methoxylated flavones eupatilin (EUP) and xanthomicrol (XAN), and the sesquiterpene zerumbone (ZER), were compared in SH-SY5Y human neuroblastoma cells to assess their potential as neuroblastoma-specific therapeutics. EUP, XAN, and ZER (2.5–100 μM) exerted marked significant cytotoxicity (MTT assay) and morphological changes after 24 h of incubation, following the order XAN > ZER > EUP > ARZ (no toxic effect). The propidium iodide fluorescence assay (PI, red fluorescence) and NucView® 488 assay (NV, green fluorescence) evidenced a significant increase in the apoptotic cell number, vs. controls, in SH-SY5Y cells pre-incubated for 2 h with the compounds, in the following order of apoptotic potency: XAN > EUP > ZER > ARZ. The PubChem database and freely accessible web tools SwissADME, pkCSM-pharmacokinetics, and SwissTargetPrediction were used to assess the physicochemical/pharmacokinetic properties and potential protein targets of the compounds. At 50 μM, a positive correlation (r = 0.917) between values of % viability reduction and % human intestinal absorption (bioavailability) was observed, indicating a marked contribution of compound membrane permeability to cytotoxicity in SH-SY5Y cells. The capacity of compounds to induce apoptosis emerged as inversely correlated to the computed lipophilicity (r = −0.885).