Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Trapika, I Gusti Made Gde Surya Chandra; Liu, Xin Tracy; Chung, Long Hoa; Lai, Felcia; Xie, Chanlu; Zhao, Yang; Cui, Shaohui; Chen, Jinbiao; Tran, Collin; Wang, Qian; Zhang, Shubiao; Don, Anthony S.; Li, George Q.; Hanrahan, Jane R.; Qi, Yanfei

doi:10.3389/fonc.2021.738078

Cited by 14 publications

(8 citation statements)

References 84 publications

(143 reference statements)

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“…Western blot analysis indicated signi cant reductions in phosphorylated JNK, p38, and ERK-1 proteins. These results concur with earlier studies demonstrating erianin capacity to hinder ERK pathway activation in diverse cancer cells, yielding various biological effects, notably anti-tumor properties [33]. Prior research supports erianin apoptosis induction, along with its capability to curb the proliferation and migration of diverse cancer cells [18,19].…”

Section: Discussionsupporting

confidence: 90%

Erianin impedes the proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells

Hu,

Kunkun

2023

Preprint

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In this study, we have investigated erianin, a natural phenolic drug that impedes proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells. Eca-109 cells were treated with different concentrations of erianin (4, 8, 12 µM) for 24 hours, and then cell proliferation, apoptosis, and metastatic markers were evaluated. Erianin-induced cytotoxicity and cell proliferation were examined using MTT and crystal violet staining techniques. The measurement of reactive oxygen species (ROS) and the study of apoptotic changes were conducted through flow cytometry. Furthermore, protein expression analyses via western blotting included an evaluation of JAK-STAT3, cell survival, cell cycle, proliferation, and apoptosis-related proteins. Moreover, erianin treatment-associated MMP expressions were studied by RT-PCR. In this study, erianin treatment induces substantial cytotoxicity and ROS production based on the concentrations in Eca-109 cells. Moreover, erianin inhibits the MAPK phosphorylation, proliferation, and metastatic protein in Eca-109 cells. STAT-3 is a crucial transcriptional factor that regulates numerous downstream proteins, such as proliferation, anti-apoptosis, and metastatic proteins. In this study, erianin treatment inhibited the protein expression of IL-6, IL-10, JAK-1, and p-STAT-3 expressions leading to induce apoptosis in Eca-109 cells. Moreover, erianin inhibited the expression of proliferation, metastatic, and anti-apoptotic markers in Eca-109 cells. Hence, erianin suppressed the JAK/STAT-3 signaling pathway and demonstrates potential as a chemotherapeutic agent for the treatment of esophageal cancer.

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Section: Discussionsupporting

confidence: 90%

Erianin impedes the proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells

Hu,

Kunkun

2023

Preprint

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“…As mentioned above, in human prostate cancer cells, antiproliferative and apoptotic effects can also be mediated by ceramide accumulation and these compounds have been suggested as possible mediators of cannabinoid action, and more specifically, of the endogenous cannabinoid anandamide [ 27 ]. Consistent with this, altered levels of intracellular ceramide have been found in both LNCaP and PC3 cells [ 51 ].…”

Section: Discussionsupporting

confidence: 65%

The Plant Derived 3-3′-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Cancer Cellular Models

Tucci

Brown

Bewick

et al. 2023

IJMS

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3-3′-Diindolylmethane (DIM) is a biologically active dimer derived from the endogenous conversion of indole-3-carbinol (I3C), a naturally occurring glucosinolate found in many cruciferous vegetables (i.e., Brassicaceae). DIM was the first pure androgen receptor antagonist isolated from the Brassicaceae family and has been recently investigated for its potential pharmacological use in prostate cancer prevention and treatment. Interestingly, there is evidence that DIM can also interact with cannabinoid receptors. In this context, by considering the well-known involvement of the endocannabinoid system in prostate cancer, we have pharmacologically characterized the properties of DIM on both CB1 and CB2 cannabinoid receptors in two human prostate cancer cell lines: PC3 (androgen-independent/androgen receptor negative) and LNCaP (androgen-dependent). In the PC3 cell line, DIM was able to activate CB2 receptors and potentially associated apoptotic pathways. On the other hand, although DIM was also able to activate CB2 receptors in the LNCaP cell line, no apoptotic effects were observed. Our evidence confirms that DIM is a CB2 receptor ligand and, moreover, it has a potential anti-proliferative effect on androgen-independent/androgen receptor-negative prostate cancer cells.

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“…Cells were treated with FFA combination for 10 days. Colonies were fixed with 4% cold paraformaldehyde, followed by crystal violet (0.5% w/v, Sigma-Aldrich, St. Louis, USA) staining [ 72 ]. Images were captured using a ChemiDoc TM Touch Imaging System (Bio-Rad Laboratories, Hercules, USA) and quantified using ImageJ software (FIJI version 1.52).…”

Section: Methodsmentioning

confidence: 99%

“…Cell cycle was examined in Huh7 cells fixed with 70% cold ethanol at 4 °C overnight. The fixed cells were then incubated with FxCycle™PI/RNase Staining Solution (Thermo Fisher, Waltham, USA) for 30 min at room temperature and analyzed using BD LSRII (BD Biosciences, Franklin Lakes, USA) [ 72 ]. G2/M phase was determined using FlowJo version 10 (BD Biosciences, Franklin Lakes, USA) in Waston (Pragmatic) mode.…”

Section: Methodsmentioning

confidence: 99%

Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein

et al. 2022

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Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC.

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Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Cited by 14 publications

References 84 publications

Erianin impedes the proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells

Erianin impedes the proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells

The Plant Derived 3-3′-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Cancer Cellular Models

Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein

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