YKL-06-061 exerts antitumor effect through G1/S phase arrest by downregulating c-Myc and inhibition of metastasis via SIK1 upregulation in pancreatic cancer DOI

Chao-Yang Zeng,

Wendie Wang,

Yue Shang

и другие.

Anti-Cancer Drugs, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

Pancreatic cancer ranks fourth among cancer-related deaths with a low 5-year overall survival rate of less than 13%. At present, treatment pancreatic is still based on chemotherapy, but the efficacy limited. Thus, novel therapeutic agent for therapy urgently needed. A library compounds was screened, and YKL-06-061, selective inhibitor salt-inducible kinases (SIKs), discovered its ability inhibiting proliferation metastasis cells in vitro reducing growth xenografts nude mice vivo . The results from transcriptome analysis showed that YKL-06-061 influenced mRNA levels many genes related to c-Myc SIK1 signals. Based this, it found induced cell cycle arrest at G1 phase decreased c-Myc, CDK4, cyclin D1 protein. same time, inhibited invasion cells, increased E-cadherin protein, lowered vimentin ZEB-1. Moreover, effectively enhanced antiproliferation gemcitabine or doxorubicin synergistic manner. Collectively, these findings implicate as promising patients cancer.

Язык: Английский

In Vitro and In Vivo Anticancer Activities of Water-Soluble Ru(II)(η6-p-cymene) Complexes via Activating Apoptosis Central Regulators and Possibilities of New Antitumor Strategies in Triple Negative Breast Cancers DOI

Shad Man,

Haojie Ren,

Yimiao Li

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

In this study, we synthesized 12 monofunctional tridentate ONS-donor salicylaldimine ligand (L)-based Ru(II) complexes with general formula [(Ru(L)(p-cymene)]+·Cl– (C1-C12), characterized by 1H NMR, 13C UV, FT-IR spectroscopy, HR-ESI mass spectrometry, and single-crystal X-ray analysis showing ligand's orientation around the center. All of these were tested for their anticancer activities in multiple cancer cells. The superior antitumor efficacy C2, C8, C11 was demonstrated reduced mitochondrial membrane potential, impaired proliferative capacity, disrupted redox homeostasis, along enhanced apoptosis through caspase-3 activation downregulation Bcl-2 expression. 4T1 breast orthotopic mouse model, assessment bioluminescence metastatic spread, tumor burden, histopathological evaluation, immunohistochemistry (IHC), hematological profiling tissue Protein expression caspase-3, cleaved TNF-α, bcl-2 that C8 treatment led to prolonged survival suppressed progression triple negative cancer.

Язык: Английский

Процитировано

1
YKL-06-061 exerts antitumor effect through G1/S phase arrest by downregulating c-Myc and inhibition of metastasis via SIK1 upregulation in pancreatic cancer DOI

Chao-Yang Zeng,

Wendie Wang,

Yue Shang

и другие.

Anti-Cancer Drugs, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

Pancreatic cancer ranks fourth among cancer-related deaths with a low 5-year overall survival rate of less than 13%. At present, treatment pancreatic is still based on chemotherapy, but the efficacy limited. Thus, novel therapeutic agent for therapy urgently needed. A library compounds was screened, and YKL-06-061, selective inhibitor salt-inducible kinases (SIKs), discovered its ability inhibiting proliferation metastasis cells in vitro reducing growth xenografts nude mice vivo . The results from transcriptome analysis showed that YKL-06-061 influenced mRNA levels many genes related to c-Myc SIK1 signals. Based this, it found induced cell cycle arrest at G1 phase decreased c-Myc, CDK4, cyclin D1 protein. same time, inhibited invasion cells, increased E-cadherin protein, lowered vimentin ZEB-1. Moreover, effectively enhanced antiproliferation gemcitabine or doxorubicin synergistic manner. Collectively, these findings implicate as promising patients cancer.

Язык: Английский

Процитировано

0