Differentiation-Inducing Activity of Hydroxycamptothecin on Cancer Stem-Like Cells Derived from Hepatocellular Carcinoma

Zhang, Yi; Song, Wenjie; Zhang, Fuqin; Liu, Weihui; Dou, Kefeng

doi:10.1007/s10620-011-1601-6

Cited by 11 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanically, microRNAs have been shown to be involved in the anti-cancer effect of natural plant extracts. miRNAs have various functions, such as induction of apoptosis [18] , anti-metastasis [19] , antiangiogenesis [20] , proliferation inhibition [21] and suppression of cancer stem-like cells [22] . Combining the microarray data with TCGA data, we identified miR-616-5p as a prominent regulator of NSCLC progression.…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways

et al. 2016

View full text Add to dashboard Cite

Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC 50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 μmol/L, respectively. At low concentrations (1-5 μmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3β and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3β/β-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or therapeutic target to inhibit metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In multiple myeloma, lenalidomide, a clinically used drug, was found to decrease the tumorigenicity and clonogenicity of SP cells through inducing phosphorylation of Akt, GSK-3α/β, MEK1, c-Jun, p53 and p70S6K (25). Hydroxycampto thecin, another anticancer agent, was shown to inhibit MHCC-97-SP cell proliferation and invasion by inducing differentiation (26).…”

Section: Discussionmentioning

confidence: 99%

Isocorydine Targets the Drug-Resistant Cellular Side Population through PDCD4-Related Apoptosis in Hepatocellular Carcinoma

Lü

Sun

Zhang

et al. 2012

Mol Med

View full text Add to dashboard Cite

Isocorydine (ICD), an anticancer agent under current evaluation, decreased the percentage of side population (SP) cells significantly in hepatocellular carcinoma (HCC) cell lines. ICD treatment sensitized cancer cells to doxorubicin (DXR), a conventional clinical chemotherapeutic drug for HCC. We found that ICD decreased the percentage of SP cells in HCC cell lines by preferentially killing SP cells. In the early stage of treatment, ICD inhibited SP cell growth by arresting cells in G2/M; later, it induced apoptosis. Our xenograft model confirmed that ICD selectively reduced the size and weight of SP-induced tumor masses in vivo. Furthermore, it was found that programmed cell death 4 (PDCD4), a tumor suppressor gene, was relatively low when expressed in SP cells compared with non-SP cells, and its expression level was remarkably elevated when cells were treated with ICD. Taken together, these data suggest that ICD is a drug that may target the SP cells of HCC.

show abstract

“…Topoisomerase inhibitors are widely used anti‐tumor agents . Indeed, camptothecin and its derivatives were earlier shown to have potent growth inhibitory activity against HCC cells and in vivo . Hydroxycamptothecin has been shown to induce functional hepatocyte‐specific markers such as albumin, HNF4 and miR‐122 while decrease the malignant state marker, AFP .…”

Section: Discussionmentioning

confidence: 99%

Integrative functional genomic delineation of the cascades of transcriptional changes involved in hepatocellular carcinoma progression

Ramesh

Ganesan

2016

Intl Journal of Cancer

View full text Add to dashboard Cite

Development of targeted therapeutics is still at its early stage for hepatocellular carcinoma (HCC) due to the incomplete understanding of the confounding regulations at signaling pathway level. In this investigation, gene co-expression-based networking and integrative functional genomic modeling of HCC mRNA profiles as signaling processes were employed to understand the complex signaling cascades involved in HCC development toward understanding the avenues for targeted therapeutics. Multiple sets of genes and molecular biological processes involved during HCC development were identified from this integrative analysis: (i) Loss of liver cellular features due to the reduced HNF4A & PPAR signaling in the early stages of HCC, (ii) activated inflammatory and stress signals in the cirrhosis stages and (iii) highly activated cellular proliferation with the activated E2F-MYC oncogenic signaling with the gain of embryonic liver stem cell-like features in the advanced stage tumors. Upon connecting these gene-sets with the established drug sensitivity-related gene signatures, targeted therapeutic strategies for the heterogeneous HCC conditions have been identified. PPAR agonist class of drugs for early stage HCC conditions, anti-inflammatory drugs for cirrhosis and topoisomerase inhibitors for the advanced HCC conditions were inferred. Integrative functional genomic analysis of HCC transcriptome profiles at the context of signaling pathways has defined the key molecular processes involved in HCC development. Further, the study highlights the stage-specific and pathway focused targeted therapeutics for HCC. These findings deserve extensive preclinical explorations toward the establishment of targeted therapeutics.Hepatocellular Carcinoma (HCC) is the second most deadly cancers and is the sixth most common cancer.1 HCC development usually occurs from cirrhotic liver followed by dysplastic lesions and leads toward HCC. 2 Current best curative options involve liver transplantation or surgical resection although rewarding only when diagnosed at early stages. Nevertheless, the recurrence and metastasis are common in patients and the 5-year survival rate is 30-40% after treatment. 3

show abstract

Differentiation-Inducing Activity of Hydroxycamptothecin on Cancer Stem-Like Cells Derived from Hepatocellular Carcinoma

Abstract: Our data suggest that a low concentration of HCPT can induce hepatocyte-specific differentiation of cancer stem-like cells from MHCC97 cells, offering a possible therapeutic strategy for the treatment of human malignancies.

Cited by 11 publications

References 35 publications

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways

Isocorydine Targets the Drug-Resistant Cellular Side Population through PDCD4-Related Apoptosis in Hepatocellular Carcinoma

Integrative functional genomic delineation of the cascades of transcriptional changes involved in hepatocellular carcinoma progression

Contact Info

Product

Resources

About