Oligandrin from Croton oligandrus (Euphorbiaceae) exhibits anti-breast cancer activity through immune-boosting mechanisms: In vitro and in vivo study

Abstract

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.