PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Kumazoe, Motofumi; Takai, Mika; Hiroi, Shun; Takeuchi, Chieri; Yamanouchi, Maasa; Nojiri, Takashi; Onda, Hiroaki; Bae, Jae‐Hoon; Huang, Yuhui; Takamatsu, Kanako; Yamashita, Shigeki; Yamada, Shuhei; Kangawa, Kenji; Takahashi, Takashi; Tanaka, Hiroshi; Tachibana, Hirofumi

doi:10.1038/s41598-017-02162-9

Cited by 33 publications

(20 citation statements)

References 47 publications

(80 reference statements)

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“…EGCG could inhibit many kinds of cancer stem cells. But whether EGCG has an inhibitory effect on osteosarcoma stem cells has not been studied yet [34][35][36]. Through subsequent experiments, we have confirmed that EGCG can partially inhibit the self-renewal ability of OSC by targeting SOX2OT V7, and significantly enhance the inhibitory effect of DOX on OSC growth.…”

Section: Disscussionsupporting

confidence: 54%

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Wang

Chen

Zhu

2018

J Exp Clin Cancer Res

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Background: Doxorubicin is the preferred chemotherapeuticdrug for osteosarcoma treatment of which clinical efficacy is limited because of its chemo-resistance and cardiac toxicity. It is necessary to develop the combination regimen with complementary molecular mechanisms to reduce the side effects and enhance sensitivity of Doxorubicin. EGCG is a polyphenol in green tea with antitumor bioactivity,which has been found that its combination with certain chemotherapeutic drugs could improve the antitumor efficiency. Methods: In this study, MTT assay was used to detect the cell growth inhibition The CD133+/CD44+ cells were isolated from U2OS and SaoS2 cell lines using magnetic-activated cell sorting and identified by flow cytometry analysis. qRT-PCR was used for determining the relative mRNA levels of key genes. Immunofluorescence was performed to evaluate the autophagy flux alterations. Self-renewal ability was accessed by sphere-forming assay. Tumorigenicity in nude mice was preformed to evaluate tumorigenicity in vivo. Results: We found that EGCG targeting LncRNA SOX2OT variant 7 produced synergistic effects with Doxorubicin on osteosarcoma cell growth inhibition. On the one hand, EGCG could reduce the Doxorubicin-induced pro-survival autophagy through decreasing SOX2OT variant 7 to improve the growth inhibition of Doxorubicin. On the other hand, EGCG could partially inactivate Notch3/DLL3 signaling cascade targeting SOX2OT variant 7 to reduce the stemness then abated drug-resistance of osteosarcoma cells.

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Section: Disscussionsupporting

confidence: 54%

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Wang

Chen

Zhu

2018

J Exp Clin Cancer Res

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“…PDE3 also plays a role in CSCs. In pancreatic cancer cells expressing 67-kDa laminin receptor-dependent cGMP inducer, a PDE3 inhibitor in combination with epigallocatechin-3-O-gallate induced cGMP, which impair CSCs properties [94]. In a separate study, cGMP was shown to suppress CD44 high pancreatic CSCs [95].…”

Section: Fatty Acidsmentioning

confidence: 98%

Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications

et al. 2020

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Tumor metastasis is the major cause of mortality from cancer. Metabolic rewiring and the metastatic cascade are highly intertwined, co-operating to promote multiple steps of cancer metastasis. Metabolites generated by cancer cells influence the metastatic cascade, encompassing epithelial-mesenchymal transition (EMT), survival of cancer cells in circulation, and metastatic colonization at distant sites. A variety of molecular mechanisms underlie the prometastatic effect of tumor-derived metabolites, such as epigenetic deregulation, induction of matrix metalloproteinases (MMPs), promotion of cancer stemness, and alleviation of oxidative stress. Conversely, metastatic signaling regulates expression and activity of rate-limiting metabolic enzymes to generate prometastatic metabolites thereby reinforcing the metastasis cascade. Understanding the complex interplay between metabolism and metastasis could unravel novel molecular targets, whose intervention could lead to improvements in the treatment of cancer. In this review, we summarized the recent discoveries involving metabolism and tumor metastasis, and emphasized the promising molecular targets, with an update on the development of small molecule or biologic inhibitors against these aberrant situations in cancer.

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“…The 67 laminin receptor (67LR) is overexpressed in various cancers, including PDACs. In PDACs overexpressing 67LR, a phosphodiesterase inhibitor (PDE3) and epigallocatechin 3- O -gallate (EGCG) in combination significantly suppressed the FOXO3-CD44 axis in pancreatic cancer stem cells [ 167 ].…”

Section: Pancreatic Cancer Stem Cellsmentioning

confidence: 99%

Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

2017

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Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments.

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PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Cited by 33 publications

References 47 publications

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications

Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

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