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. - 2025
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.
Yaya, Joël Abel Gbaweng; Zingue, Stephane; Offermann, Anneet al.
2025 • In Journal of Ethnopharmacology, 338 (Pt 2), p. 119073
[en] [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 potent cytotoxicity and apoptosis-inducing activity, making it a promising lead for discovering a new anticancer drug.
Research center :
CMMI - Centre de Recherche en Microscopie et Imagerie Médicale
Disciplines :
Oncology Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others Life sciences: Multidisciplinary, general & others
Author, co-author :
Yaya, Joël Abel Gbaweng; Department of Chemistry, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon, Centre for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies, P.O. Box 13033, Ngaoundere, Cameroon
Zingue, Stephane; Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, P.O. Box 1364, Yaounde, Cameroon, Institute of Pathology, University Hospital Schleswig-Holstein, 23538, Luebeck, Germany. Electronic address: stephane.zingue@fmsb-uy1.cm
Offermann, Anne; Institute of Pathology, University Hospital Schleswig-Holstein, 23538, Luebeck, Germany, Gerhard-Domagk Institute of Pathology, University Hospital Münster, Germany
Feunaing Toko, Roméo; Department of Chemistry, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon
Kang, Duan; Institute of Pathology, University Hospital Schleswig-Holstein, 23538, Luebeck, Germany
Bapong, Elisée; Department of Chemistry, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon
Henoumont, Céline ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Chimie générale, organique et biomédicale
Laurent, Sophie ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Chimie générale, organique et biomédicale
Sailer, Verena-Wilbeth; Institute of Pathology, University Hospital Schleswig-Holstein, 23538, Luebeck, Germany
Kirfef, Jutta; Institute of Pathology, University Hospital Schleswig-Holstein, 23538, Luebeck, Germany
Talla, Emmanuel; Department of Chemistry, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon
Perner, Sven; Institute of Pathology, University Hospital Schleswig-Holstein, 23538, Luebeck, Germany
Language :
English
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.
R550 - Institut des Sciences et Technologies de la Santé R100 - Institut des Biosciences
Funding text :
The authors are grateful to the International Foundation for Science (IFS) which supported this work through the grant number I1-F-6564-1 to Dr. YAYA G. Abel Joel. This work has been performed with the support from OPCW (Organization for the Prohibition of Chemical Weapons) to Prof. Dr. Stephane Zingue (Grant N\u00B0 OPCW 188/22 1/3 INS). We thank the bioprofiling platform supported by the European Regional Development Fund and the Walloon Region, Belgium.
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