Synergistic Effects of Ethanol Extracts of Eleutherine bulbosa (Dayak Onion) and Tamoxifen on TNF-α and Breast Tissue Morphology in a Mouse Model of Breast Cancer

Abstract

Breast cancer is the most common malignancy in women globally, influenced by inflammatory mediators like Tumor Necrosis Factor-alpha (TNF-α). Although, tamoxifen is a standard therapy for breast cancer, its effectiveness is often limited by adverse side effects and development of resistance. This study aimed to investigate the synergistic potential of tamoxifen and Eleutherine bulbosa ethanol extract in modulating TNF-α levels and improving breast tissue morphology in mouse model of breast cancer. Breast cancer was induced in five of six BALB/c mouse groups (n = 36) by oral administration of 7,12-dimethylbenz(a)anthracene (DMBA) for 28 days, while the negative control remained uninduced. Following induction, the mice received oral treatments with E. bulbosa extract (180 mg/kg) and tamoxifen (10 mg/kg), administered either individually or in sequential combination for 14 days. Serum TNF-α levels were assessed on day 15 using ELISA, and breast tissue morphology was examined histologically. All treatment groups showed a significant TNF-α reduction compared to the positive control (p < 0.001). The sequential administration of tamoxifen followed by E. bulbosa produced the most pronounced reduction in TNF-α levels (53.32 ± 4.94 ng/mL), approaching that observed in the Negative Control group (40.10 ± 5.10 ng/mL). This effect was significantly greater than that achieved with E. bulbosa extract alone (87.48 ± 3.70 ng/mL) or tamoxifen monotherapy (65.68 ± 6.51 ng/mL). Histopathological analysis showed significant improvements in breast tissue morphology, closely resembling normal histological architecture. In conclusion, tamoxifen combined with E. bulbosa extract showed superior efficacy in reducing TNF-α and restoring breast tissue.