Major depression is an important complication in patients with breast cancer, but is an underrecognized and undertreated condition in this population. The Baihe Zhimu Tang (BZ formula) is a traditional Chinese formula consisting of Lilium brownii var. viridulum Baker (L. brownii) and Anemarrhena asphodeloides (A. asphodeloides) Bunge that is used for the treatment of depression. However, the interaction between tamoxifen and BZ formula is frequently overlooked by traditional and alternative medical doctors. In the present study, the influence of BZ formula on the effectiveness of tamoxifen in breast cancer in mice and the effects of tamoxifen on the antidepressant effect of BZ formula and its major components mangiferin and timosaponin BII in mice were investigated. Identification of the major components of BZ formula was performed using fast HPLC-tandem mass spectrometry (HPLC-MS/MS). The main flavonoids and saponins in A. asphodeloides were determined by HPLC-UV and HPLC-ELSD, separately. The antidepressant efficacy of BZ formula was evaluated using a mouse tail-suspension test. The effects of BZ formula on the antineoplastic activity of tamoxifen were performed in a mouse xenograft model of human breast cancer MCF-7 cells. P450 activity was determined using microsomal incubations by HPLC-MS/MS. Measurement of serum concentrations of tamoxifen and its metabolites was used by HPLC-MS/MS. BZ formula attenuated the effectiveness of tamoxifen treatment of breast cancer and reduced the concentrations of endoxifen and 4-OH-tamoxifen in tumor-bearing mice. Of two of the major components of BZ formula, the antidepressant effect of mangiferin, but not timosaponin BII, was significantly inhibited by tamoxifen in mice. BZ formula and its component mangiferin also significantly inhibited CYP450 enzyme activity in rat liver microsomes. BZ formula attenuated the effectiveness of tamoxifen in treatment of breast cancer in mice by influencing CYP450 enzymes. The present study laid a foundation for the treatment of patients with breast cancer and depression by BZ formula or other Chinese herbal formulas containing A. asphodeloides.

Introduction: Breast Cancer (BC) is one of the most prevalent malignant tumors in women. The incidence of estrogen receptor-positive (ER+) breast cancer is as high as 70%, and it is increasing. Amorphophalli rhizoma (APR) has the potential to be used in breast cancer. Aims: The objectives of the present study were to explore the impact of different APR extracts on the proliferation, migration, and invasion of ER+BC and to investigate their possible mechanism at the molecular level. Methods: Various extracts of APR were prepared in different solvents, such as petroleum ether, ethyl acetate, n-butanol, and water. ER+ T47D breast cancer cell lines were acquired and uti-lized to assess the effect of APR extracts on ER+ BC. Cell viability was assessed using the cell counting kit8 (CCk8) method, while anti-invasive and migratory effects were examined by transwell and wound healing assay. All the extracts were initially screened, and the ethyl acetate fraction (APR-EA) was found to be the most effective. Ultra High-Performance Liquid Chro-matography (UHPLC) of APR-EAE extract revealed the presence of various phytochemicals, such as succinic acid, 2-methoxy resorcinol, penicillic acid, morphine, salicylic acid, α-linolenic acid, and linolenic acid. Flow cytometry, western blot, and immunohistochemistry were used to explore molecular mechanisms. Results: APR-EA demonstrated anti-proliferative, anti-migratory, and anti-invasive effects on the ER+ T47D cell line. Thus, APR-EAE might inhibit the expression of P-PI3K/PI3K and P-Akt/Akt proteins, which subsequently represses the expression of ERα. This inhibition affects the downstream expression of the proteins CDK4 and Bcl-2, which are linked to cell growth and apoptosis. Conclusion: Additionally, APR-EA might increase the expression of P21 and Bax proteins, which are associated with cell cycle arrest and apoptosis. Overall, these effects contribute to the anti-ER+ breast cancer properties of APR-EA.