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Marine Drugs
Volume 21
Issue 6
10.3390/md21060345
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Article

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

by
Sirorat Janta
1,
Kanta Pranweerapaiboon
1,2,
Pornpun Vivithanaporn
3,
Anuchit Plubrukarn
4,
Arthit Chairoungdua
5,
Prachayaporn Prasertsuksri
1,
Somjai Apisawetakan
6 and
Kulathida Chaithirayanon
1,*
1
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
2
Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12120, Thailand
3
Chakri Naruebodindra Medical Institute, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10540, Thailand
4
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 09112, Thailand
5
Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
6
Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Wattana, Bangkok 10110, Thailand
*
Author to whom correspondence should be addressed.
Mar. Drugs 2023, 21(6), 345; https://doi.org/10.3390/md21060345
Submission received: 10 May 2023 / Revised: 1 June 2023 / Accepted: 2 June 2023 / Published: 3 June 2023
(This article belongs to the Special Issue Bioactive Compounds from Sea Cucumbers)
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Abstract

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.
Keywords: RUNX1; holothurin A; EMT; metastasis; prostate cancer RUNX1; holothurin A; EMT; metastasis; prostate cancer
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MDPI and ACS Style

Janta, S.; Pranweerapaiboon, K.; Vivithanaporn, P.; Plubrukarn, A.; Chairoungdua, A.; Prasertsuksri, P.; Apisawetakan, S.; Chaithirayanon, K. Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway. Mar. Drugs 2023, 21, 345. https://doi.org/10.3390/md21060345

AMA Style

Janta S, Pranweerapaiboon K, Vivithanaporn P, Plubrukarn A, Chairoungdua A, Prasertsuksri P, Apisawetakan S, Chaithirayanon K. Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway. Marine Drugs. 2023; 21(6):345. https://doi.org/10.3390/md21060345

Chicago/Turabian Style

Janta, Sirorat, Kanta Pranweerapaiboon, Pornpun Vivithanaporn, Anuchit Plubrukarn, Arthit Chairoungdua, Prachayaporn Prasertsuksri, Somjai Apisawetakan, and Kulathida Chaithirayanon. 2023. "Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway" Marine Drugs 21, no. 6: 345. https://doi.org/10.3390/md21060345

APA Style

Janta, S., Pranweerapaiboon, K., Vivithanaporn, P., Plubrukarn, A., Chairoungdua, A., Prasertsuksri, P., Apisawetakan, S., & Chaithirayanon, K. (2023). Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway. Marine Drugs, 21(6), 345. https://doi.org/10.3390/md21060345

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