Blockage of STAT3 Signaling Pathway by Morusin Induces Apoptosis and Inhibits Invasion in Human Pancreatic Tumor Cells

Chulwon, Kim; Kim, Jin Ho; Oh, Eun Young; Nam, Dongwoo; Lee, Seok-Geun; Lee, Junhee; Kim, Sung Hoon; Shim, Bum Sang; Ahn, Kwang Seok

doi:10.1097/mpa.0000000000000496

Cited by 30 publications

(23 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 This compound has been found to engage in a myriad of biological functions, including anti-inflammatory, antioxidative and antitumor activities. [16][17][18] For instance, Morusin was reported to attenuate LPS-induced proinflammatory responses in RAW264.7 cells. 19 Additionally, an in vivo study revealed that Morusin ameliorates 2, 4, 6-trinitrobenzene sulfonic acid sodium salt (TNBS)induced colitis in rats.…”

Section: Introductionmentioning

confidence: 99%

<p>Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway</p>

Jia

Zhang

et al. 2020

DDDT

View full text Add to dashboard Cite

Osteoarthritis (OA) is one of the most common degenerative joint diseases in the world, characterized primarily by the progressive degradation of articular cartilage. Accumulating evidence has shown that Morusin, a flavonoid derived from the root bark of Morus alba (mulberry) plants, exerts unique protective properties in several diseases. However, its effects on OA, specifically, have not yet been characterized. Methods: In this study, we evaluated the anti-inflammatory effect of Morusin on mouse chondrocytes and its underlying mechanism in vitro. In addition, the protective effect of Morusin on destabilization of the medial meniscus (DMM) model was also explored in vivo. Results: In vitro, IL-1β-induced activation of inflammatory factors (TNF-α, IL-6, INOS and COX2) was dramatically suppressed by Morusin. Further, Morusin treatment inhibited the expression of ADAMTS5 and metalloproteinase (MMPs), both of which regulate extracellular matrix degradation. Morusin also decreased IL-1β-induced p65 phosphorylation and IκBα degradation. In vivo, degradation of the articular cartilage following surgical DMM, which mimicked OA pathology, was abrogated following treatment with Morusin, thus demonstrating a protective effect in the DMM model. Conclusion: Herein, we demonstrate that Morusin reduces the OA inflammatory response in vitro and protects against articular cartilage degradation in vivo potentially via regulation of the NF-κB pathway. Hence, Morusin may prove to be an effective candidate for novel OA therapeutic strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway</p>

Jia

Zhang

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“…Additionally, morusin suppressed the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) signaling pathways, which modulate the expression of proteins involved in the invasion process in human SK-Hep1 hepatocellular carcinoma cells (23). In addition, blockage of the STAT3 signaling pathway by morusin induced apoptosis and inhibited invasion in human pancreatic tumor cells (AsPC-1, BxPC-3, MIA PaCa-2, and PANC-1) (24). Morusin can also exert inhibitory effects on stem cell growth and migration in human cervical cancer (25).…”

Section: Introductionmentioning

confidence: 99%

Morusin suppresses A549 cell migration and induces cell apoptosis by downregulating the expression of COX‑2 and VEGF genes

Yin

Wang

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

The present study aimed to examine the inhibitory effects of morusin on the human lung cancer cell line A549. Various doses of morusin were applied to A549 cells and the effects were assessed by wound‑healing and MTT assays, flow cytometry analysis of apoptosis, a mitochondrial membrane potential assay and RT‑PCR. The results indicated that the concentrations of 10 and 30 µg/ml morusin significantly inhibited A549 cells and signs of apoptosis were observed. In addition, the wound‑healing assay results revealed that morusin inhibited cell migration. Flow cytometry analysis demonstrated that the rates of apoptosis were 16.46, 55.80 and 70.80% following treatment with 1, 10 and 30 µg/ml of morusin, respectively, and that the mitochondrial membrane potentials also decreased with the increase of morusin. Furthermore, morusin increased the antioxidant activities of the A549 cells. RT‑PCR analysis revealed that the expression levels of COX‑2 and VEGF were downregulated following morusin treatment. In conclusion, morusin significantly inhibited the proliferation of the lung cancer cell line A549, and may have affected the invasion and migration of the cells by downregulating the expression of tumor angiogenesis‑related genes.

show abstract

“…This compound has various biological activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-obesity, and anti-microbial, although most studies have focused on the anti-tumor effects [ 4 ]. Morusin dramatically suppresses the growth of different tumor types including breast cancer [ 5 ], glioblastoma [ 6 ], pancreatic cancer [ 7 ], hepatocarcinoma [ 8 ], prostate cancer [ 9 ], and gastric cancer [ 10 ]. Also, it inhibits the inflammatory response by suppressing the COX activity and iNOS expression [ 11 ], while strong antibacterial activity against Gram-positive bacteria was detected after morusin treatment [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Morusin Functions as a Lipogenesis Inhibitor as Well as a Lipolysis Stimulator in Differentiated 3T3-L1 and Primary Adipocytes

et al. 2018

View full text Add to dashboard Cite

Conflicting results for morusin activity during adipogenic differentiation are reported in 3T3-L1 adipocytes and cancer cells. To elucidate the influence of morusin on fat metabolism, their anti-obesity effects and molecular mechanism were investigated in 3T3-L1 cells and primary adipocytes. Morusin at a dose of less than 20 µM does not induce any significant change in the viability of 3T3-L1 adipocytes. The accumulation of intracellular lipid droplets in 3T3-L1 adipocytes stimulated with 0.5 mM 3-isobutyl-1-methylxanthine, 1 µM dexamethasone, 10 µg/mL insulin in DMEM containing 10% FBS (MDI)-significantly reduces in a dose-dependent manner after morusin treatment. The phosphorylation level of members in the MAP kinase signaling pathway under the insulin receptor downstream also decrease significantly in the MDI + morusin-treated group compared to MDI + vehicle-treated group. Also, the expression of adipogenic transcription factors (PPARγ and C/EBPα) and lipogenic proteins (aP2 and FAS) are significantly attenuated by exposure to the compound in MDI-stimulated 3T3-L1 adipocytes. Furthermore, the decrease in the G0/G1 arrest of cell cycle after culturing in MDI medium was dramatically recovered after co-culturing in MDI + 20 µM morusin. Moreover, morusin treatment induces glycerol release in the primary adipocytes of SD rats and enhances lipolytic protein expression (HSL, ATGL, and perilipin) in differentiated 3T3-L1 adipocytes. Overall, the results of the present study provide strong evidence that morusin inhibits adipogenesis by regulating the insulin receptor signaling, cell cycle and adipogenic protein expression as well as stimulating lipolysis by enhancing glycerol release and lipolytic proteins expression.

show abstract

Blockage of STAT3 Signaling Pathway by Morusin Induces Apoptosis and Inhibits Invasion in Human Pancreatic Tumor Cells

Abstract: Morusin is a novel blocker of STAT3 activation and thus may have potential in negative regulation of growth and metastasis of pancreatic tumor cells.

Cited by 30 publications

References 47 publications

<p>Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway</p>

<p>Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway</p>

Morusin suppresses A549 cell migration and induces cell apoptosis by downregulating the expression of COX‑2 and VEGF genes

Morusin Functions as a Lipogenesis Inhibitor as Well as a Lipolysis Stimulator in Differentiated 3T3-L1 and Primary Adipocytes

Contact Info

Product

Resources

About