Tris(dibenzylideneacetone)dipalladium(0) (Tris DBA) Abrogates Tumor Progression in Hepatocellular Carcinoma and Multiple Myeloma Preclinical Models by Regulating the STAT3 Signaling Pathway

Tris(dibenzylideneacetone)dipalladium(0) (Tris DBA) Abrogates Tumor Progression in Hepatocellular Carcinoma and Multiple Myeloma Preclinical Models by Regulating the STAT3 Signaling Pathway

STAT3 is an oncogenic transcription factor that controls the expression of genes associated with oncogenesis and malignant progression. Persistent activation of STAT3 is observed in human malignancies, including hepatocellular carcinoma (HCC) and multiple myeloma (MM). Here, we have investigated the...

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Autores principales: Loukik Arora, Chakrabhavi Dhananjaya Mohan, Min Hee Yang, Shobith Rangappa, Amudha Deivasigamani, Alan Prem Kumar, Ajaikumar B. Kunnumakkara, Manoj Garg, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Tahani Awad Alahmadi, Kanchugarakoppal S. Rangappa, Kam Man Hui, Gautam Sethi, Kwang Seok Ahn
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
Tris DBA
STAT3 signaling inhibitor
orthotopic
xenograft
SHP2
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Acceso en línea:https://doaj.org/article/276d22a07db44cb8b9e9fcf7579c394a
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Sumario:STAT3 is an oncogenic transcription factor that controls the expression of genes associated with oncogenesis and malignant progression. Persistent activation of STAT3 is observed in human malignancies, including hepatocellular carcinoma (HCC) and multiple myeloma (MM). Here, we have investigated the action of Tris(dibenzylideneacetone) dipalladium 0 (Tris DBA) on STAT3 signaling in HCC and MM cells. Tris DBA decreased cell viability, increased apoptosis, and inhibited IL-6 induced/constitutive activation of STAT3, JAK1, JAK2, and Src in HCC and MM cells. Tris DBA downmodulated the nuclear translocation of STAT3 and reduced its DNA binding ability. It upregulated the expression of SHP2 (protein and mRNA) to induce STAT3 dephosphorylation, and the inhibition of SHP2 reversed this effect. Tris DBA downregulated the expression of STAT3-driven genes, suppressed cell migration/invasion. Tris DBA significantly inhibited tumor growth in xenograft MM and orthotopic HCC preclinical mice models with a reduction in the expression of various prosurvival biomarkers in MM tumor tissues without displaying significant toxicity. Overall, Tris DBA functions as a good inhibitor of STAT3 signaling in preclinical HCC and MM models.

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