Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells<i>in vitro</i>and<i>in vivo</i>by modulating multiple cellular pathways

Tai, Yang; Liu, Jin; Yang, Mali; Huang, Ning; Zhong, Yueling; Zeng, Ting; Rong, Wei; Wu, Zhongjun; Xiao, Cui; Cao, Xiaohua; Li, Min-Hui; Li, Limei; Han, Bin; Yu, Xiaoping; Li, Hua; Zou, Qiang

doi:10.18632/oncotarget.10584

Cited by 19 publications

(22 citation statements)

References 56 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cucurbitacins exhibit various biological and pharmacological activities, including antitumor, anti-inflammatory, hepatoprotective, and cytotoxic effects [ 18 – 20 ]. Particularly, most cucurbitacins, such as A, B, E, and I, affect the growth of various human cancer cell lines including breast, prostate, and brain cancer cells [ 21 – 23 ]. In addition, recent study also demonstrated that cucurbitacin B and I exert the preventive effects of adipocyte differentiation by modulating STAT3 signaling pathway [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H₂O₂‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Yang

Kim

2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Cucurbitacin I, a triterpenoid natural compound, exhibits various pharmacological properties, including anticancer, anti-inflammatory, and hepatoprotective properties. However, antioxidant effects of cucurbitacin I in cardiac cells are currently unknown. In the present study, we assessed the preventive effects of cucurbitacin I against the oxidative stress in H9c2 cardiomyoblasts. To evaluate antioxidant effects of cucurbitacin I in H9c2 cardiomyoblasts, H2O2-treated H9c2 cells were pretreated with various concentrations of the cucurbitacin I. Cell viability, reactive oxygen species (ROS) production, and apoptosis were determined to elucidate the protective effects of cucurbitacin I against H2O2-induced oxidative stress in H9c2 cells. In addition, we assessed the mitochondrial functions and protein expression levels of mitogen-activated protein kinases (MAPKs). Cucurbitacin I prevented the cells against cell death and ROS production and elevated the antioxidant protein levels upon oxidative stress. Furthermore, cucurbitacin I preserved the mitochondrial functions and inhibited the apoptotic responses in H2O2-treated cells. Cucurbitacin I also suppressed the activation of MAPK proteins (extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38). Collectively, cucurbitacin I potentially protects the H9c2 cardiomyoblasts against oxidative stress and further suggests that it can be utilized as a therapeutic agent for the prevention of oxidative stress in cardiac injury.

show abstract

Section: Introductionmentioning

confidence: 99%

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H₂O₂‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Yang

Kim

2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Cell lysates from SupM2, an ALK-positive anaplastic large cell lymphoma cell line known to have a high pSTAT3 expression [ 29 ], were used as the positive control. To explore the possible activators of STAT3 in 3D culture, we checked the expression level of several cytokines which are known to induce STAT3 phosphorylation in MM: IL6, IL21 and IL10 [ 30 , 31 , 32 ]. As shown in Figure S3 , the expression of all three cytokines in U266 cells increased by 1.5–2.5 folds after 1 day of 3D culture compared to cells in conventional culture.…”

Section: Resultsmentioning

confidence: 99%

Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

Huang

Molavi

Alshareef

et al. 2018

Cancers

View full text Add to dashboard Cite

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (phospho-STAT3 or pSTAT3), which was absent in MM cells cultured conventionally, became detectable after 1–2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in 3D culture can generate results that are more representative of the disease.

show abstract

“…It has been reported that the CuB-induced suppression of cell proliferation is associated with cofilin activation (dephosphorylation) ( Yang et al, 2017 ). Thus, we investigated the effect of CuE on Caco-2 cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

Cucurbitacin E Inhibits Proliferation and Migration of Intestinal Epithelial Cells via Activating Cofilin

Song

Wang

et al. 2018

Front. Physiol.

View full text Add to dashboard Cite

The proliferation and migration of intestinal epithelial cell is important to the barrier integrity of intestinal epithelium. Cucurbitacin E (CuE) is one of the tetracyclic triterpenoids extracted from the cucurbitaceae that has been shown to inhibit cancer cell growth, tumor angiogenesis and inflammatory response. Nevertheless, the role of Cucurbitacin E in regulating the proliferation and migration of intestinal epithelial cells remain unclear. In this study, the human intestinal epithelial cell line Caco-2 was treated with CuE and the effects of CuE on cell cycle, proliferation, migration and actin dynamics in Caco-2 cells were investigated successively. We found that CuE significantly inhibited the cell proliferation and migration, inducing the cell cycle arrest in G2/M phase and disrupting the actin dynamic balance in Caco-2 cells. Finally, we showed that CuE inhibited cofilin phosphorylation by suppressing the phosphorylation of both LIM kinase (LIMK)1 and LIMK2 in vitro, resulting in the activation of cofilin, which is closely associated with cell proliferation and migration. Therefore, our studies provided the first evidence that CuE inhibited the proliferation and migration of intestinal epithelial cells via activating cofilin, and CuE is a potential candidate in intestinal disease therapy.

show abstract

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cellsin vitroandin vivoby modulating multiple cellular pathways

Cited by 19 publications

References 56 publications

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H₂O₂‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H₂O₂‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

Cucurbitacin E Inhibits Proliferation and Migration of Intestinal Epithelial Cells via Activating Cofilin

Contact Info

Product

Resources

About

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cellsin vitroandin vivoby modulating multiple cellular pathways

Cited by 19 publications

References 56 publications

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H2O2‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H2O2‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

Cucurbitacin E Inhibits Proliferation and Migration of Intestinal Epithelial Cells via Activating Cofilin

Contact Info

Product

Resources

About

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H₂O₂‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

Cucurbitacin I Protects H9c2 Cardiomyoblasts against H₂O₂‐Induced Oxidative Stress via Protection of Mitochondrial Dysfunction