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

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.