Bioguided identification of daucosterol, a compound that contributes to the cytotoxicity effects of Crateva adansonii DC (capparaceae) to prostate cancer cells.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Crateva adansonii DC (Capparaceae) is a shrub used to treat tumors in Cameroon. In our previous reports, a Crateva adansonii dichloromethane-methanol (DCM/MeOH) extract was shown to prevent chemically induced tumors in Wistar rats.

AIM OF STUDY:

To determine the bioactive principle of Crateva adansonii extract and to elucidate its underlying mechanism.

MATERIALS AND METHODS:

An activity-guided fractionation was realized using MTT assay. To investigate if the bioactive compound daucosterol (CA2) accounted for the previously observed anticancer effects of the C. adansonii extract, it was tested on cell growth, cell proliferation, cell cycle, cell death mechanism and cell migration. In addition, cell cycle- and apoptosis-regulating proteins were assessed by Western blotting.

RESULTS:

Daucosterol (CA2), a steroid saponin, was identified as major anticancer principle of the C. adansonii extract. Daucosterol significantly inhibited LNCaP, DU145 and PC3 prostate carcinoma cell growth and proliferation at the optimal concentration of 1 μg/mL. It also significantly increased the number of late apoptotic (DU145) and apoptotic (PC3) cells. The number of cells in S phase increased in DU145, while the number of G0/G1 cells decreased. Cell cycle proteins (cdk1, pcdk1, cyclin A and B) were down-regulated in DU145 and PC3 cells, whereas only cdk2 was down-regulated in PC3 cells. Moreover, the anti-apoptotic Akt, pAKT and Bcl-2 proteins were down-regulated, while the pro-apoptotic protein Bax was up-regulated. CA2 induced anti-metastatic effects by decreasing chemotaxis and cell migration, while it increased cell adhesion to fibronectin and collagen matrix.

CONCLUSION:

These results suggest that daucosterol is the major active principle responsible at least in part for the anticancer effect of the extract of Crateva adansonii.

• Authors: Stéphane Zingue, Abel Joël Gbaweng Yaya, Thomas Michel, Derek Tantoh Ndinteh, Jochen Rutz, Florence Auberon, Sebastian Maxeiner, Felix K-H Chun, Alembert Tiabou Tchinda, Dieudonné Njamen, Roman A Blaheta
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 247 Pg. 112251 (Jan 30 2020) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 31560992 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• Sitosterols
• Proto-Oncogene Proteins c-akt
• lyoniside

Topics

• Apoptosis (drug effects)
• Biological Assay
• Cameroon
• Capparaceae (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemical Fractionation
• Chemotaxis (drug effects)
• Down-Regulation (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• Male
• Medicine, African Traditional (methods)
• Neoplasm Invasiveness (prevention & control)
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Prostatic Neoplasms (drug therapy, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Sitosterols (isolation & purification, pharmacology)
• Up-Regulation (drug effects)