Jin Hana, Lee Won Sup, Eun So Young, Jung Ji Hyun, Park Hyeon-Soo, Kim Gonsup, Choi Yung Hyun, Ryu Chung Ho, Jung Jin Myung, Hong Soon Chan, Shin Sung Chul, Kim Hye Jung
Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
Int J Oncol. 2014 Oct;45(4):1629-37. doi: 10.3892/ijo.2014.2535. Epub 2014 Jul 4.
Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.
桑色素是一种存在于无花果和其他桑科植物中的黄酮类化合物,具有多种生物学活性,如抗氧化、抗炎和抗癌作用。然而,桑色素的抗癌作用,尤其是其抗转移作用尚不清楚。因此,在本研究中,我们研究了桑色素对高转移性人乳腺癌细胞的抗癌作用。我们的结果表明,桑色素在低剂量(50µM)时就能显著抑制高转移性MDA-MB-231乳腺癌细胞的集落形成能力,且无细胞毒性。此外,桑色素使MDA-MB-231细胞形态从间充质形态转变为上皮形态,并以剂量依赖的方式抑制MDA-MB-231细胞的侵袭。桑色素降低了MDA-MB-231细胞基质金属蛋白酶-9(MMP-9)的分泌和间充质标志物N-钙黏蛋白的表达,提示桑色素可能抑制上皮-间质转化(EMT)过程。此外,桑色素显著降低了Akt的磷酸化,抑制Akt信号通路可显著降低MDA-MB-231细胞的侵袭。在体内异种移植小鼠模型中,桑色素抑制了MDA-MB-231癌细胞的进展。综上所述,我们的研究结果表明,桑色素至少部分通过抑制Akt激活,对高转移性乳腺癌细胞的癌症进展和EMT过程具有抑制作用。本研究为桑色素可能对转移性乳腺癌具有抗癌作用提供了证据。