Yang Shu-Yu, Li Jen Ying, Huang Guan-Jhong, Sridharan Badrinathan, Wang Jen-Shu, Chang Kai-Ming, Lee Meng-Jen
Department of Chinese Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
Evid Based Complement Alternat Med. 2021 May 19;2021:6665949. doi: 10.1155/2021/6665949. eCollection 2021.
(Bge.) Kitag. (CP) is an important medicinal herb used in Chinese herbal medicine, with a variety of biological activities including anticancer property. In this study, we explored the water extract of CP, for its anticancer effects against breast cancer cells with different mutation types. Cells were grouped as untreated (Control); CP direct treatment (dir-CP); Conditioned medium from CP treated (sup-CP), and untreated cells (sup-Control). Effects of dir-CP and sup-CP were compared to corresponding untreated cells on cytotoxicity, cell migration, and protein expression (cleaved caspase-3, caspase-9, and MMP-2 and 9). CP treatment showed time-dependent decrease in cell number of MDA-MB-231 and SK-Br-3 (both ER(-) PR(-)), while the decrease in cell number was not as significant in MCF-7 and ZR-75-1 cells (both ER(+) PR(+)). sup-CP treatment inhibited the cell migration of MDA-MB-231 and MCF-7 (Her2(-)) in a 24 h scratch assay. Our data suggested that ER(-) PR(-) cells are more sensitive to the CP in terms of direct cytotoxicity, which is not regulated by caspase-3. CP inhibited the migration of the two Her2(-) cells, and this correlated with MMP-2 regulation. The migration of ER(-) PR(-) cells was more sensitive to conditioned medium with CP treatment than to direct CP, and this is not regulated by MMP-2. Our data suggested that CP has anticancer potential on various breast cancer cells through different mechanisms and is specifically effective in inhibiting the migration of the triple negative MDA-MB-231. Our data provide insight into the mechanism of CP against breast cancer progression and would benefit the medical practitioners in better management with CP usage.
(白芨)紫花三叉大白及(CP)是一种在中国草药中使用的重要草药,具有多种生物活性,包括抗癌特性。在本研究中,我们探索了CP的水提取物对不同突变类型乳腺癌细胞的抗癌作用。细胞分为未处理组(对照);CP直接处理组(dir-CP);CP处理后的条件培养基组(sup-CP)和未处理细胞组(sup-对照)。将dir-CP和sup-CP对相应未处理细胞在细胞毒性、细胞迁移和蛋白质表达(裂解的半胱天冬酶-3、半胱天冬酶-9以及基质金属蛋白酶-2和9)方面的作用进行了比较。CP处理显示MDA-MB-231和SK-Br-3(均为雌激素受体(ER)阴性、孕激素受体(PR)阴性)的细胞数量呈时间依赖性减少,而在MCF-7和ZR-75-1细胞(均为ER阳性、PR阳性)中细胞数量的减少不那么显著。在24小时划痕试验中,sup-CP处理抑制了MDA-MB-231和MCF-7(人表皮生长因子受体2(Her2)阴性)的细胞迁移。我们的数据表明,就直接细胞毒性而言,ER阴性、PR阴性细胞对CP更敏感,且不受半胱天冬酶-3调节。CP抑制了两种Her2阴性细胞的迁移,这与基质金属蛋白酶-2的调节相关。ER阴性、PR阴性细胞的迁移对CP处理后的条件培养基比直接CP更敏感,且不受基质金属蛋白酶-2调节。我们的数据表明,CP通过不同机制对各种乳腺癌细胞具有抗癌潜力,并且在抑制三阴性MDA-MB-231的迁移方面特别有效。我们的数据为CP对抗乳腺癌进展的机制提供了见解,并将有助于医生更好地使用CP进行治疗。