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Kerstinginone, a new flavanone derivative from Commiphora kerstingii Engl. (Burseraceae) with potent apoptosis-inducing activity and inhibition of AKT/mTOR signaling pathway in non-sensitive prostate cancer cells.

Bibliographic Details
Title: Kerstinginone, a new flavanone derivative from Commiphora kerstingii Engl. (Burseraceae) with potent apoptosis-inducing activity and inhibition of AKT/mTOR signaling pathway in non-sensitive prostate cancer cells.
Authors: Yaya, Joël Abel Gbaweng, Zingue, Stephane, Offermann, Anne, Feunaing Toko, Roméo, Kang, Duan, Bapong, Elisée, Henoumont, Céline, Laurent, Sophie, Sailer, Verena-Wilbeth, Kirfef, Jutta, Talla, Emmanuel, Perner, Sven
Contributors: CMMI - Centre de Recherche en Microscopie et Imagerie Médicale, M108 - Chimie générale, organique et biomédicale, R550 - Institut des Sciences et Technologies de la Santé, R100 - Institut des Biosciences
Source: Journal of Ethnopharmacology, 338 (Pt 2), 119073 (2025-02-10)
Publisher Information: Elsevier Ireland Ltd
Publication Year: 2025
Subject Terms: Apoptosis, Cell growth, Commiphora kerstingii, Kerstingilactone, Kerstinginone, Prostate cancer, Proto-Oncogene Proteins c-akt, Plant Extracts, TOR Serine-Threonine Kinases, Antineoplastic Agents, Phytogenic, Flavanones, Humans, Male, Cell Line, Tumor, Cell Proliferation/drug effects, Phytogenic/pharmacology, Phytogenic/isolation & purification, Phytogenic/chemistry, Cell Survival/drug effects, Cell Movement/drug effects, Flavanones/pharmacology, Flavanones/isolation & purification, Plant Leaves/chemistry, Plant Bark/chemistry, PC-3 Cells, Apoptosis/drug effects, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/pathology
Description: peer reviewed ; [en] ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora kerstingii Engl is a tree which is 20-30 m in height and commonly called "ararrabi" in Hausa. It is found in the Sahelian region (Cameroon, Chad, and Nigeria) where it is utilized for the treatment of several ailments including cancer. AIM OF THE STUDY: This study was aimed at investigating the chemical constituents and cytotoxic effect of extracts and isolates from the stem barks and leaves of C. kerstingii. MATERIALS AND METHODS: Using classical chromatography technique coupled with spectroscopic analysis and literature information, ten (10) compounds were isolated from C. kerstingii stem barks and leaves, out of which two [kerstingilactone (3) and kerstinginone (10)] were new. To evaluate their potential cytotoxic effect, the impact on cell viability, growth, and proliferation was assessed using MTT and CCK-8 assays. Cell death mechanisms were analyzed via flow cytometry, and Western blotting was utilized to examine the expression of specific regulatory proteins. Furthermore, anti-metastatic properties were investigated through assays on cell migration, adhesion, and chemotaxis. RESULTS: Among the tested compounds, 2 (Masticadienonic Acid) and 10 (kerstinginone) exhibited significant dose-dependent inhibition of PC3 and LNCaP cell growth. Compound 2 displayed optimal inhibitory effects within a concentration range of 10-40 μg/mL, while compound 10 demonstrated potent growth inhibition at concentrations of 2.5-10 μg/mL. Both compounds suppressed cell proliferation and the formation of clones. Specifically, compound 2 induced apoptosis solely in the androgen-sensitive LNCaP prostate cancer cells, whereas compound 10 induced a stronger and concentration-dependent apoptotic response in both PC3 and LNCaP cells, resulting in approximately 50-70% apoptotic cells. It also induced potent cell migration/invasion arrest at concentrations ranging from 2.5 to 5 μg/mL and increased cell adhesion to the extracellular matrix. CONCLUSION: Kerstinginone exhibits ...
Document Type: article in journal/newspaper
Language: English
ISSN: 0378-8741
1872-7573
Relation: https://api.elsevier.com/content/article/PII:S0378874124013722?httpAccept=text/xml; urn:issn:0378-8741; urn:issn:1872-7573; https://orbi.umons.ac.be/handle/20.500.12907/53640; info:hdl:20.500.12907/53640; info:pmid:39522846
DOI: 10.1016/j.jep.2024.119073
Availability: https://orbi.umons.ac.be/handle/20.500.12907/53640
https://hdl.handle.net/20.500.12907/53640
https://orbi.umons.ac.be/bitstream/20.500.12907/53640/1/1-s2.0-S0378874124013722-main.pdf
https://doi.org/10.1016/j.jep.2024.119073
Rights: open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess
Accession Number: edsbas.A8A37D89
Database: BASE
Description
ISSN:03788741
18727573
DOI:10.1016/j.jep.2024.119073