Hanafi, MMM, Yaakob, H, Gibbons, S and Prieto, JM (2023) In Vitro Pro-Apoptotic and Anti-Migratory Effects of Marantodes pumilum (syn. Labisia pumila) Extracts on Human Prostate Cancer Cell Lines: Bioguided Isolation of 5-Henicosene-1-yl-resorcinol. Plants, 12 (7). ISSN 2223-7747

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Abstract

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Marantodes pumilum Blume Kuntze plant extracts on prostate cancer cells, identify the active compound/s, and characterize their mechanism of action. The crude methanolic extract was partitioned into n-hexane (MPh), chloroform (MPc), and aqueous (MPa) extracts. Antiproliferative fractions (IC50 < 30 μg/mL based on SRB staining of LNCaP and PC3 cell lines) were further fractionated. Active compound/s were identified using spectroscopic methods. In vitro mechanistic studies on PC3 cells included: annexin V-FITC staining, mitochondrial membrane potential (MMP) depolarization measurements, the activity of caspases 3 and 7, nuclear DNA fragmentation, cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, Alox-5, VEGF-A, CXCR4, and CXCL12 mRNA gene expression via RT-PCR, 2D migration (scratch assay), and 3D invasion (Boyden chamber). MPc extract was the most active, inducing cell death (p < 0.05) via apoptosis, as evidenced by nuclear DNA fragmentation and an increase in MMP depolarization (p < 0.05) as well as the activation of caspases 3/7 (MPc p < 0.01) in both PC3 and LNCaP cell lines. In addition, MPc upregulated Bax and Smac/DIABLO, downregulated Bcl-2 (p < 0.05), and inhibited ALOX-5 mRNA gene expression (p < 0.001). MPc was not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Moreover, MPc inhibited migration and invasion of PC3 cells (p < 0.01). These effects were accompanied by the downregulation of both VEGF-A and CXCL-12 gene expressions (p < 0.001). A monounsaturated 5-alkyl resorcinol was isolated as the active compound in the MPc extract and identified as 5-henicosene-1-yl-resorcinol.

Item Type:	Article
Uncontrolled Keywords:	Marantodes pumilum; apoptosis; invasion; migration; prostate cancer
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	MDPI AG
SWORD Depositor:	A Symplectic
Date Deposited:	21 Jul 2023 08:27
Last Modified:	21 Jul 2023 08:30
DOI or ID number:	10.3390/plants12071576
URI:	https://researchonline.ljmu.ac.uk/id/eprint/20463

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