In Vitro and In Vivo Effects of Xanthorrhizol on Human Breast Cancer MCF-7 Cells Treated With Tamoxifen

Abstract

IntroductionBreast cancer is the most frequently diagnosed cancer among women internationally and is the second highest cause of cancer-related death. The incidence of breast cancer varies hugely around the world, both in developed and developing countries (1). In Thailand, breast cancer is currently the most common cancer and involves 43% of all cancers diagnosed in women (2).Estrogen receptors, when binding with estrogen, have important physiological roles in cardiovascular protection, the humoral immune response, neuroprotection, and bone remodeling. In breast cancer cells, estrogen and/or progesterone receptor status is highly linked to the patients' prognosis after surgery (3). Although many selective estrogen receptor modulators have been studied (4, 5), at present, hormonal therapy with tamoxifen is considered a gold standard when preventing tumor recurrence in women with hormone-responsive breast cancer. Tamoxifen, a non-steroidal selective estrogen receptor modulator, is commonly used for the hormone therapy of receptors-positive breast cancers in pre- Chang-Gung Memorial Hospital, Taoyuan, 333, Taiwan, ROC Received February 2, 2014; Accepted May 8, 2014 Abstract. This study investigated the herb-drug interaction of xanthorrhizol and tamoxifen in human breast cancer cells. Using MCF-7 cell line as an in vitro model, the herb-drug interaction between xanthorrhizol and tamoxifen was measured by MTT assay, luciferase reporter assay, and cell cycle analysis. The effects of xanthorrhizol on growth/autophagy related signaling were determined by immunostaining, western blotting, and real time RT-PCR. Additionally, the in vivo effect of xanthorrhizol and tamoxifen on athymic nude mice implanted with MCF-7 cells was evaluated. When MCF-7 cells were co-treated with tamoxifen and xanthorrhizol, there were no significant changes in terms of cell number, luciferase activity, percentage S-phase cells and LC3-II expression. However, using the MCF-7 implanted nude mice model, it was possible to detect significantly increased tumor volumes, a larger tumor size, and increased protein expression of P38 and P27(Kip1) in the xanthorrhizol + tamoxifen group compared to the tamoxifen-alone group. It can be concluded that while there is no significant herb-drug interaction between xanthorrhizol and tamoxifen in vitro, there is such an interaction in tumor-bearing mice, which provides important information that affects breast cancer treatment translational research. In Vitro and In Vivo Effects of Xanthorrhizol on Human Breast Cancer MCF-7 Cells Treated With Tamoxifen

Xanthorrhizol: a review of its pharmacological activities and anticancer properties

“…Based on the estrogenic [ 20 , 33 ] and anti-estrogenic activities [ 12 ] reported, we suggest that XNT may act as a potent phytoestrogen with beneficial therapeutic potential. According to Tham et al, the partial estrogenic/anti-estrogenic behaviour is a common characteristic of phytoestrogens [ 53 ].…”

“…Previous studies evaluated that XNT has antimicrobial [ 15 , 16 , 19 , 22 – 25 ], anti-inflammatory [ 10 , 17 , 26 , 27 ], antioxidant [ 5 , 17 ], antihyperglycemic [ 6 ], antihypertensive [ 21 , 28 ], antiplatelet [ 29 ], nephroprotective and hepatoprotective [ 30 – 32 ], estrogenic and antiestrogenic properties [ 20 , 33 ]. These pharmacological activities are summarized in Table 1 .…”

“…XNT has been known to possess estrogenic activity in estrogen receptor (ER)-positive MCF-7 cells during the state of hormone starvation [ 20 , 33 ]. It has been reported that XNT treatment upregulated ER target gene expression, trefoil factor 1 (pS2) and promoted the interaction of ER-estrogen response elements (EREs) in MCF-7 cells.…”

“…Recent in vitro and in vivo studies of XNT-tamoxifen interaction conducted by Noomhorm and colleagues have contributed new information on breast cancer treatment translational research. XNT was found to interact with tamoxifen increasing MCF-7 proliferative activity in vivo [ 33 ].…”

“…Tamoxifen is a common non-steroidal selective ER modulator used to treat pre-menopausal and post-menopausal women with receptor-positive, ER(+)/progesterone receptor (PR)(+) breast cancers [ 33 ]. Although this hormonal therapy is recognized as a gold standard in hindering tumor recurrence of hormone-responsive breast cancer, it always results both mild and serious unfavorable side effects.…”