Vocational High School of Islahiye, Gaziantep University, Gaziantep, Turkey.
Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey.
Mol Cell Biochem. 2018 Feb;439(1-2):189-198. doi: 10.1007/s11010-017-3147-1. Epub 2017 Aug 9.
5-Fluorouracil (5-FU) is a widely used chemotherapy agent for breast cancer, although drug resistance is a critical issue regarding the use of this agent in the disease. Calcium signaling is a well-known main cause of proliferation and apoptosis in breast cancer cells. Although previous studies have implicated TRPV1 inhibitor, anticancer, and apoptotic roles of Hypericum perforatum (HPer) in several cells, the synergistic inhibition effects of HPer and 5-FU in cancer and the stimulation of ongoing apoptosis have not yet been clarified in MCF-7 cells. Therefore, we investigated the apoptotic and antioxidant properties of 5-FU with/without HPer through activation of TRPV1 in MCF-7 cells. The MCF-7 cells were divided into four groups: the control group, the HPer-treated group (0.3 mM), the 5-FU-treated group (25 μM), and the 5-FU+HPer-treated group. The intracellular free calcium ion concentration ([Ca]) increased with 5-FU treatments, but they decreased with the HPer and HPer+5-FU treatments. The [Ca] is further decreased in the four groups by TRPV1 channel antagonist (capsazepine and 0.01 mM) treatments. However, mitochondrial membrane depolarization and apoptosis levels, and the PARP1, caspase 3, and caspase 9 expression levels were increased by 5-FU treatment, although the values were decreased by the HPer and 5-FU+HPer treatments. Cell viability level was also decreased by 5-FU treatment. In conclusion, antitumor and apoptosis effects of 5-FU are up-regulated by activation of TRPV1 channels, but its action was down-regulated by HPer treatment. It seems that HPer cannot be used for increasing the antitumor effect of 5-FU through modulation of the TRPV1.
5-氟尿嘧啶（5-FU）是一种广泛用于乳腺癌的化疗药物，但在该疾病中使用该药物时，耐药性是一个关键问题。钙信号是乳腺癌细胞增殖和凋亡的主要原因之一。虽然之前的研究表明贯叶连翘（HPer）的 TRPV1 抑制剂、抗癌和促凋亡作用在几种细胞中，但 HPer 和 5-FU 在癌症中的协同抑制作用以及对正在进行的凋亡的刺激作用尚未在 MCF-7 细胞中阐明。因此，我们通过激活 MCF-7 细胞中的 TRPV1 研究了 5-FU 与/或 HPer 的促凋亡和抗氧化特性。将 MCF-7 细胞分为四组：对照组、HPer 处理组（0.3 mM）、5-FU 处理组（25 μM）和 5-FU+HPer 处理组。随着 5-FU 处理，细胞内游离钙离子浓度（[Ca]）增加，但随着 HPer 和 HPer+5-FU 处理，[Ca]降低。用 TRPV1 通道拮抗剂（辣椒素和 0.01 mM）处理进一步降低了四组中的 [Ca]。然而，线粒体膜去极化和凋亡水平以及 PARP1、caspase 3 和 caspase 9 的表达水平随着 5-FU 处理而增加，尽管 HPer 和 5-FU+HPer 处理降低了这些水平。细胞活力水平也随着 5-FU 处理而降低。总之，TRPV1 通道的激活上调了 5-FU 的抗肿瘤和促凋亡作用，但 HPer 处理下调了其作用。似乎 HPer 不能通过调节 TRPV1 来增加 5-FU 的抗肿瘤作用。
