Oligandrin from Croton oligandrus (Euphorbiaceae) exhibits anti-breast cancer activity through immune-boosting mechanisms: In vitro and in vivo study
Stéphane Zingue,
Yannick Stéphane Fotsing Fongang,
Eric Roger Ossomba,
Vanneck Tatsinda,
Kevine Kamga Silihe,
William Defo Mbou,
Balotin Fogang,
René Essomba,
Jean Rodolphe Chouna,
Dieudonné Njamen,
Lawrence Ayong
Affiliations
Stéphane Zingue
Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde, 1, P.O. Box 1364, Yaounde, Cameroon; Corresponding author. Basic and Clinical Cancer Research Unit, Department of Pharmacotoxicology and Pharmacokinetics, University of Yaounde 1, P.O. Box 1364, Yaounde, Cameroon.
Yannick Stéphane Fotsing Fongang
Department of Chemistry, Higher Teachers' Training College, University of Maroua, P.O. Box 55, Maroua, Cameroon
Eric Roger Ossomba
Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde, 1, P.O. Box 1364, Yaounde, Cameroon
Vanneck Tatsinda
Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon
Kevine Kamga Silihe
Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde, 1, P.O. Box 1364, Yaounde, Cameroon; Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé, 1, P.O. Box 812, Yaoundé, Cameroon
William Defo Mbou
Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde, 1, P.O. Box 1364, Yaounde, Cameroon; Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé, 1, P.O. Box 812, Yaoundé, Cameroon
Balotin Fogang
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé, 1, P.O. Box 812, Yaoundé, Cameroon; Malaria Research Unit, Centre Pasteur, Yaoundé, Cameroon
René Essomba
Department of Microbiology, Parasitology, Hematology and Infectious Diseases, Faculty of Medicine and Biomedical Sciences, University of Yaounde, 1, P.O. Box 1364, Yaounde, Cameroon
Jean Rodolphe Chouna
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé, 1, P.O. Box 812, Yaoundé, Cameroon
Dieudonné Njamen
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé, 1, P.O. Box 812, Yaoundé, Cameroon
Lawrence Ayong
Malaria Research Unit, Centre Pasteur, Yaoundé, Cameroon; Corresponding author.
Aim: Recent developments in cancer research indicate that cancer is a manifestation of immune system dysfunction. Many natural anticancer agents developed recently possess immune-modulatory properties. In our ongoing pursuit of anticancer alternatives, we evaluated the immune-modulatory potential of oligandrin, an ent-pimarane type diterpenoid from Croton oligatrus. Methods: we assessed on Breast cancer patients’ peripheral blood mononuclear cells (PBMCs) were isolated to assess the effect of oligandrin (0.5, 1, 10, 100, 200 mg/mL) in vitro using the Ficoll-histopaque density centrifugation method. The parameters that were assessed included, PBMC viability and cytokine (IL-6, IL-12, IL-10, EGF, TNF-α, INF-γ) production. In vivo, we chemically induced breast cancer using DMBA (50 mg/kg BW) in Wistar rats, then treated them with oligandrin (1 mg/kg BW) or standards (tamoxifen 3.3 mg/kg; letrozole 1 mg/kg) for 20 weeks. The parameters that were evaluated included, tumor burden, volume, incidence, histopathology, antioxidant, and inflammatory status. Results: Oligandrin (1, 10, 100 and 200 μg/mL) significantly increased (p < 0.05) PBMC cell number 24 h after incubation. In vivo, it induced 62.5 % tumor incidence reduction compared to DMBA rats (100 %). Oligandrin significantly protected (p < 0.001) rats against increased tumor burden, mass and volume, which was accompanied by a significant antioxidant effect [increment of GSH (p < 0.01) and SOD (p < 0.001)]. Oligandrin prevented high-grade adenocarcinomas according to SBR stratification and significantly reduced pro-inflammatory cytokine levels (IL-6, IL-12) while increasing anti-inflammatory cytokine levels (INF-γ). Conclusion: Oligandrin is reported for the first time to protect against breast cancer onset and this effect seems to be at least in part attributable to its immune-boosting capacity.
