<i>In vitro</i> and <i>in silico</i> studies of holothurin A on androgen receptor in prostate cancer

Pranweerapaiboon, Kanta; Garon, Arthur; Seidel, Thomas; Janta, Sirorat; Plubrukarn, Anuchit; Chaithirayanon, Kulathida; Langer, Thierry

doi:10.1080/07391102.2021.1975562

Cited by 8 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study [ 19 ], HA exerted a cytotoxicity in LNCaP cells, reporting an IC 50 at 24 and 48 h of 1.98 and 1.59 µM, respectively. The same concentration at 0.25–1 µM in LNCaP cells that were also affected by HA showed morphological changes in the cells and nuclei ( Figure 2 C).…”

Section: Resultsmentioning

confidence: 95%

“…It firstly was isolated from Actynopyga agassizi [ 15 ], but its full structure was elucidated by Kitagawa et al on the sample isolated from Holothuria leucospilota [ 16 ] ( Figure 1 ) and has been characterized for the presence of various biological activities [ 17 , 18 ]. Of note, our previous study addressed that HA had a substantial cytotoxic effect on the androgen-positive LNCaP cell line in accordance with the reduction of the androgen receptor expression, resulting in the downregulation of the prostate-specific antigen [ 19 ]. However, the anticancer effect of HA against PCa remains unknown, particularly in terms of the EMT for the metastasis cascade.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway

et al. 2023

Self Cite

View full text Add to dashboard Cite

Due to the challenge of prostate cancer (PCa) management, there has been a surge in efforts to identify more safe and effective compounds that can modulate the epithelial–mesenchymal transition (EMT) for driving metastasis. Holothurin A (HA), a triterpenoid saponin isolated from Holothuria scabra, has now been characterized for its diverse biological activities. However, the mechanisms of HA in EMT-driven metastasis of human PCa cell lines has not yet been investigated. Moreover, runt-related transcription factor 1 (RUNX1) acts as an oncogene in prostate cancer, but little is known about its role in the EMT. Thus, the purpose of this study was to determine how RUNX1 influences EMT-mediated metastasis, as well as the potential effect of HA on EMT-mediated metastasis in endogenous and exogenous RUNX1 expressions of PCa cell lines. The results demonstrated that RUNX1 overexpression could promote the EMT phenotype with increased EMT markers, consequently driving metastatic migration and invasion in PC3 cell line through the activation of Akt/MAPK signaling pathways. Intriguingly, HA treatment could antagonize the EMT program in endogenous and exogenous RUNX1-expressing PCa cell lines. A decreasing metastasis of both HA-treated cell lines was evidenced through a downregulation of MMP2 and MMP9 via the Akt/P38/JNK-MAPK signaling pathway. Overall, our approach first demonstrated that RUNX1 enhanced EMT-driven prostate cancer metastasis and that HA was capable of inhibiting the EMT and metastatic processes and should probably be considered as a candidate for metastasis PCa treatment.

show abstract

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The molecular anchoring conformation between holothurin as the most potent compound and phytate as a comparison compound. Holothurin is a compound belonging to the saponin group, which was reported to have bioactive properties as antifungal [6], anticancer [4], and antibacterial [13]. This research hoped can be used as a scientific basis for further investigations on a laboratory scale.…”

Section: Discussionmentioning

confidence: 94%

“…Based on the screening of oral bioavailability and drug-like parameters using the Lipinski Rules, five compounds were obtained: holothurin, arguside, miliariside, nobiliside, and virescenoside. These compounds have been reported to have efficacy in the clinical field, such as holothurin was reported to have activity as an inhibitor of androgen receptors in prostate cancer [4], as an antischistosomal [5], and as an antifungal [6]. In contrast, Nobiliside was reported as a neuraminidase inhibitor from Clostridium perfingens bacteria [7].…”

Section: Identification Of Active Compounds In Sea Cucumbermentioning

confidence: 99%

Analysis of Sea Cucumber Metabolites as Phytate Inhibitor in Human ZiP Transporter: Molecular Docking Study

Syahputra¹,

Gustini²,

Louisa³

et al. 2023

Proceedings of the 1st International Conference for Health Research – BRIN (ICHR 2022)

View full text Add to dashboard Cite

One of the causes of zinc deficiency is decreased zinc intake or impaired absorption of zinc which causes zinc bioavailability to decrease in the blood. Phytate is one of the compounds found in food that can interfere with zinc absorption in the human digestive system. The formation of a zinc complex with phytate affects zinc absorption through the human ZiP transporter (hZiP). Sea cucumber has also long been used as a dietary supplement in the East Asian region which helps maintain body health. However, there has not been much research on the potential of sea cucumber metabolites as phytate inhibitors that inhibit zinc absorption in the digestive system. The result obtained from molecular docking is that sea cucumber metabolite has the potential to inhibit the binding of phytates in ZiP2 and ZiP4 membrane proteins that act as zinc transporters from extracellular to intracellular. The metabolites in sea cucumber that have the potential as phytate inhibitors in the ZiP2 membrane protein are Holothurin, Arguside, Miliariside, Nobiliside, and Virescenoside. In the smoldering protein ZiP4, the six compounds also have the potential to inhibit phytate. Based on the molecular docking analysis, holothurin has potency as a phytate inhibitor, evidenced by binding energy and conformation in the binding site. Visualization analysis described that the holothurin precisely binds in phytate binding site in protein receptor. In addition, literature reported, that holothurin has potency as antiviral, antibacterial, and anticancer. The sea cucumber with active metabolites is one of the important marine commodities for maintaining human health and supplementation nutrition.

show abstract

“…To examine the ability of andrographolide to prevent SH-SY5Y cell death from MPP + exposure, SH-SY5Y cells (8000 cells/well) were cultured in 96-well plates for 24 h in a humidified 5% CO 2 atmosphere at 37 • C. Cells were incubated with Andro that was dissolved in dimethyl sulfoxide (DMSO for cell culture; Sigma-Aldrich, USA) at designated concentrations for 24 h. After that, the solution was removed and treated with 1.5 mM of MPP + for 24 h. Ultimately, cell viability was determined by adding 5 mg/mL MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Sigma-Aldrich, USA) for 2 h. At the indicated time, the supernatant was discarded, and formazan crystals were dissolved by adding 100 µL of dimethyl sulfoxide (DMSO; Sigma-Aldrich, USA). The absorbance was read by a microplate reader (Versamax Spectrophotometer, MA, USA) at 570 nm and 690 nm as modified from [48]. The percentage of cell viability was calculated in comparison with the untreated group.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Neuroprotection of Andrographolide against Neurotoxin MPP+-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities

Prasertsuksri

Kraokaew

Pranweerapaiboon

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Parkinson’s disease (PD) is associated with dopaminergic neuron loss and alpha-synuclein aggregation caused by ROS overproduction, leading to mitochondrial dysfunction and autophagy impairment. Recently, andrographolide (Andro) has been extensively studied for various pharmacological properties, such as anti-diabetic, anti-cancer, anti-inflammatory, and anti-atherosclerosis. However, its potential neuroprotective effects on neurotoxin MPP+-induced SH-SY5Y cells, a cellular PD model, remain uninvestigated. In this study, we hypothesized that Andro has neuroprotective effects against MPP+-induced apoptosis, which may be mediated through the clearance of dysfunctional mitochondria by mitophagy and ROS by antioxidant activities. Herein, Andro pretreatment could attenuate MPP+-induced neuronal cell death that was reflected by reducing mitochondrial membrane potential (MMP) depolarization, alpha-synuclein, and pro-apoptotic proteins expressions. Concomitantly, Andro attenuated MPP+-induced oxidative stress through mitophagy, as indicated by increasing colocalization of MitoTracker Red with LC3, upregulations of the PINK1–Parkin pathway, and autophagy-related proteins. On the contrary, Andro-activated autophagy was compromised when pretreated with 3-MA. Furthermore, Andro activated the Nrf2/KEAP1 pathway, leading to increasing genes encoding antioxidant enzymes and activities. This study elucidated that Andro exhibited significant neuroprotective effects against MPP+-induced SH-SY5Y cell death in vitro by enhancing mitophagy and clearance of alpha-synuclein through autophagy, as well as increasing antioxidant capacity. Our results provide evidence that Andro could be considered a potential supplement for PD prevention.

show abstract

In vitro and in silico studies of holothurin A on androgen receptor in prostate cancer

Cited by 8 publications

References 30 publications

Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway

Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway

Analysis of Sea Cucumber Metabolites as Phytate Inhibitor in Human ZiP Transporter: Molecular Docking Study

Neuroprotection of Andrographolide against Neurotoxin MPP+-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities

Contact Info

Product

Resources

About