Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells

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• 作者：Tae-Wook Chung^a ; ¹ ; ^{chungtw@hanmail.net} ; Hyunju Choi^b ; ¹ ; ^{chj204@skku.edu} ; Ji-Min Lee^b ; ^jml@skku.edu ; Sun-Hyung Ha^b ; ^{sunghyungha@skku.edu} ; Choong-Hwan Kwak^b ; ^{kwak@skku.edu} ; Fukushi Abekura^b ; ^{pokusa6@hotmail.com} ; Jun-Young Park^b ; ^{wnsdud2057@naver.com} ; Young-Chae Chang^c ; ^{ycchang@cu.ac.kr} ; Ki-Tae Ha^a ; ^{haggis@pnu.ac.kr} ; Seung-Hak Cho^d ; ^{skcho38@hotmail.com} ; Hyeun Wook Chang^e ; ^{hwchang@yu.ac.kr} ; Young-Choon Lee^f ; ^{yclee@dau.ac.kr} ; Cheorl-Ho Kim^a ; ^{chkimbio@skku.edu}
• 关键词：OD ; Oldenlandia diffusa ; MMP ; matrix metalloproteinase ; ICAM-1 ; intercellular adhesion molecule-1 ; MOD ; methanol extracts of OD ; BOD ; buthanol extracts of OD ; PMA ; phorbol myristate acetate ; ECM ; extracellular matrix ; PARP ; ADP-ribose polymerase ; FBS ; fatal bovine serum ; TBS-T ; Tris-Buffered Saline Tween-20 ; HRP ; horseradish peroxidase
• 刊名：Journal of Ethnopharmacology
• 出版年：2017
• 出版时间：4 January 2017
• 年：2017
• 卷：195
• 期：Complete
• 页码：309-317
• 全文大小：1031 K
• 卷排序：195

文摘

Oldenlandia diffusa (OD) has long been known as an apoptotic inducer in breast tumors in ethnomedicine.Aim of the studyTo scientifically confirm the anti-breast cancer effects of water, methanol (MeOH) and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)−1 and intracellular signaling in MCF-7 breast cancer cells.Materials and methodsMeOH extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their ability to inhibit phorbol myristate acetate (PMA)-induced matrix metalloproteinase (MMP)−9 and intercellular adhesion molecule (ICAM)−1 expressions in MCF-7 human breast cancer cells. Additionally, transwell migration, invasion and transcriptional activity were assessed. Results of immunofluorescence confocal microscopy for translocation of NF-κB and p-ERK and p-p38 were also checked. Finally, apoptotic signals including processed caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined.ResultsMOD and BOD specifically inhibited PMA-induced MMP-9 expression as well as invasive and migration potential via ICAM-1. The inhibitory activity was also based on the suppressed transcriptional activity in MCF-7 breast cancer cells. Results of immunofluorescence confocal microscopy showed that translocation of NF-κB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD activated apoptosis-linked proteins including enzymatically active forms of processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with increased expression of mitochondrial apoptotic protein, Bax and decreased expression of Bcl-2.ConclusionThe results indicate that OD as an anti-metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and NF-κB, thus reducing the invasion capacity of MCF-7 breast cancer cells through inhibition of MMP-9 and ICAM-1 expression and plays an important role in the regulation of breast cancer cell apoptosis.