Magnolol suppressed cell migration and invasion and induced cell apoptosis via inhibition of the NF-κB signaling pathway by upregulating microRNA-129 in multiple myeloma

Abstract

Multiple myeloma (MM) is incurable cancer in the blood system. Magnolol is an effective component against various cancers. This study tried to investigate the effect and mechanism of magnolol on MM via regulating miR-129. Human normal plasma cells (nPCs) and MM cells U266 and LP1 were used in this study, accompanied by treatment of magnolol. The miR-129 inhibitor was transfected into U266 and LP1 cells during experiments. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were tested by wound healing assay and Transwell assay. And Annexin-V-FITC/PI assay was utilized to assess cell apoptosis. miR-129, miR-1271-5p, miR-342-3p, and miR-124-3p expressions were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blot was adopted to evaluate Cyclin D1, matrix metalloprotein (MMP)-7, MMP-9, phosphorylation (p)-p65, and p65 protein levels. In U266 and LP1 cells, with magnolol concentration increasing, cell viability, migration, and invasion rates, Cyclin D1, MMP-7, and MMP-9 expressions decreased, while cell apoptosis rose. And magnolol increased the miR-129 expression in MM cells. Besides, miR-129 inhibitor antagonized the above-mentioned effect of magnolol and partly offset the magnolol-induced decrease of p-p65 expression, as well as the ratio of p-p65 to p65 in U266 and LP1 cells. Magnolol suppressed cell migration and invasion and induced cell apoptosis via inhibiting NFpathway activation, by upregulating miR-129 in MM.

Magnolol Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells through JNK1/2 and p38 Pathways

“…Moreover, several studies have revealed that JNK1/2 plays an anti-tumor role in oral cancer and emphasizes its positive role in apoptosis [34][35][36]. Numerous studies have also reported that magnolol inhibits cancer progression [14] or induces apoptosis [13,37] by regulating multiple cellular signaling pathways. Su et al reported that magnolol induces colorectal cancer apoptosis through both extrinsic/intrinsic pathways via PKCδ and NF-κB signaling [14].…”

“…Su et al reported that magnolol induces colorectal cancer apoptosis through both extrinsic/intrinsic pathways via PKCδ and NF-κB signaling [14]. Moreover, in multiple myeloma, magnolol induced cell apoptosis and inhibited cell migration by upregulating miR-129 and inhibiting NF-κB pathway activation [13]. Chen et al demonstrated that magnolol induced apoptosis by activating the ERK1/2 and p38 pathways in esophagus cancer KYSE150 cells [38].…”

“…Numerous previous in vitro and in vivo studies have demonstrated that magnolol has cancer chemo-preventive and inhibiting properties through different molecular mechanisms [11,12]. Jin et al reported that magnolol could suppress cell migration and induced cell apoptosis via the inhibition of the nuclear factor-κB (NF-κB) signaling pathway in human multiple myeloma cells [13]. Su et al observed that magnolol might, via extrinsic/intrinsic pathways, cause apoptosis in colorectal cancer [14].…”

Magnolol as a Potential Anticancer Agent: A Proposed Mechanistic Insight

“…NF-κB is activated by the phosphorylation-induced degradation of IκBs, which facilitates the dissociation of NF-κB from IκB family proteins in cytoplasm [ 67 ]. In various cancer types, magnolol exerted the inhibitory effect on NF-κB activity, which is demonstrated by studies of breast cancer [ 15 ], cholangiocarcinoma [ 17 ], colon cancer [ 23 ], liver cancer [ 34 , 36 ], lung cancer [ 39 ], myeloma [ 44 ], ovarian cancer [ 48 ] and skin cancer [ 57 ] ( Table 1 and Figure 2 ). For the majority of cases, the inactivation of NF-κB signaling induced by magnolol was to block the phosphorylation of IκBα and/or p65 subunit of NF-κB.…”

“…In recent years, magnolol has exhibited the antiproliferative property against various cancer types. Magnolol effectively inhibited tumor cell growth in bladder cancer [ 13 , 14 ], breast cancer [ 15 , 16 ], cholangiocarcinoma [ 17 ], colon cancer [ 18 , 19 , 20 , 21 , 22 , 23 ], esophagus cancer [ 24 ], fibrosarcoma [ 25 ], gallbladder cancer [ 26 ], gastric cancer [ 27 ], glioblastoma [ 28 , 29 , 30 , 31 , 32 ], leukemia [ 25 ], liver cancer [ 21 , 33 , 34 , 35 , 36 ], lung cancer [ 37 , 38 , 39 , 40 ], lymphoma [ 41 ], melanoma [ 25 , 42 , 43 ], myeloma [ 44 ], oral carcinoma [ 45 , 46 ], osteosarcoma [ 47 ], ovarian cancer [ 48 ], pancreatic cancer [ 49 ], prostate cancer [ 50 , 51 , 52 , 53 ], renal cancer [ 54 , 55 ], skin cancer [ 56 , 57 ] and thyroid cancer [ 58 ] (…”