Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor‐positive breast and prostate cancer cells

Abstract

The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor‐positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST‐1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug‐treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects.

Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer

“…Furthermore, hydralazine and enzalutamide as single agents also affected the PCa cells growth capacity. This corroborates previous results of the single agents in ovarian [40], breast [33], cervical [41,42], and prostate [25,26,32,35,43] cancer. In agreement with other studies [35,38,39], enzalutamide individually increased the percentage of LNCaP and C4-2 cells in the G0/G1 phase, while decreasing the percentage of LNCaP cells in the G2/M and S phase.…”

“…Additionally, as both hydralazine [33,34] and enzalutamide [35][36][37] were shown to promote an apoptotic response in various tumor models, the effect of their combination was also assessed in PCa cells. An increased apoptotic response was detected upon the combined treatment in LNCaP and C4-2, but not in PC-3 cells.…”

The expression profiles of apoptosis-related genes induced usnic acid in SK-BR-3 breast cancer cell

“…13,14 Eskiler et al investigated the effects of UA and tamoxifen or enzalutamide on MCF-7 breast cancer cells and LNCaP prostate cancer cells. 15 The examined cancer cells have been treated with UA combined with tamoxifen or enzalutamide or tamoxifen and enzalutamide. According to study result, they determined a combination of drugs with UA can be considered as potential therapeutic treatment.…”

“…According to study result, they determined a combination of drugs with UA can be considered as potential therapeutic treatment. 15 Qi et al showed that (þ)-UA takes part in inducing ROS production by reducing Nrf2 stability in a way of stimulating PI3K/Akt pathway. 16 The success of chemotherapy application for patients with late-stage metastatic breast cancer is dependent on cells being able to maintain their ability to undergo apoptosis.…”

“…18 There are many studies that determine the apoptotic effect of UA. 10,11,15,16,[19][20][21][22] In these studies, the apoptotic effect of UA was generally determined by flow cytometry and Western blot methods, and in the literature there are no studies in which the apoptotic effect is defined on mRNA level of UA on breast cancer cells. We showed more reliable results by analyzing data based on gene expression modification after applied to UA on breast cancer by quantitative real-time polymerase chain reaction (qRT-PCR).…”