Users Online: 180
Ahead of print
Export selected to
Most cited articles *
Most popular articles
Most cited articles
Show all abstracts
Show selected abstracts
Export selected to
Ursolic acid and quercetin: Promising anticancer phytochemicals with antimetastatic and antiangiogenic potential
Dharambir Kashyap, Hardeep Singh Tuli, Vivek Kumar Garg, Suhasini Bhatnagar, Anil K Sharma
January-March 2018, 1(1):9-15
Despite available treatments, the incidence of the cancer is increasing and known to be a major cause of mortality worldwide. Plant-derived terpenoids and flavonoids are considered as promising therapeutic molecules, possessing a range of medicinal properties. These phytochemicals have been used as therapeutic agents for the treatment of the various chronic infections. Terpenoids and flavonoids, particularly ursolic acid (UA) and quercetin (Quer), respectively, are emerging as effective antitumor molecules with minimal cytotoxic effects on the normal body tissues. The regulatory role of these molecules in apoptosis, angiogenesis, invasion, or metastasis has been well documented in earlier studies. Angiogenesis and metastasis are the two important hallmarks for the survival of tumor and are responsible for 50% mortality in the cancer patients. Tumor angiogenesis and metastasis have been found to be significantly inhibited in the presence of UA and Quer. Evidence suggested that these phytochemicals inhibit the initiator and progressive cytokines, chemokines, and growth factors such as matrix metalloproteinases involved in extracellular matrix remodeling during tumor metastasis. In addition, the angiogenesis-associated factors such as hypoxia-inducible factor-α and vascular endothelial growth factor/vascular endothelial growth factor receptor have also been downregulated by UA and Quer. In the present review, molecular targets of UA and Quer, in tumor metastasis and angiogenesis, have been summarized.
[Mobile Full text]
Treatment with Src inhibitor dasatinib results in elevated metastatic potential in the 4T1 murine mammary carcinoma model
Veronica S Hughes, Dietmar W Siemann
January-March 2018, 1(1):30-36
The src inhibitor dasatinib has been widely studied as an antimetastatic agent. The aims of this study were to examine the effect of Src inhibition on the metastatic potential of the 4T1 murine mammary carcinoma.
Src is a nonreceptor tyrosine kinase well known to contribute to the metastatic potential of tumor cells. It does so through alteration of signaling pathways important to metastasis. Elevated levels of Src are common in many cancer types and have been correlated with tumor progression and poor patient prognosis.
This study examined whether disruption of the Src signaling pathway could inhibit metastasis formation.
Settings and Design:
The Src inhibitor dasatinib was evaluated
using the highly metastatic 4T1 murine mammary adenocarcinoma cell line.
assays included growth curve, Western blot, migration, and invasion assays.
assays included intradermal and tail vein injection models.
Statistical Analysis Used:
data were analyzed using one-way ANOVA with Dunnett's multiple comparisons in GraphPad Prism 6.0.
data were analyzed using GraphPad Prism 6.0, using the Wilcoxon matched pairs test.
Dasatinib is effective at inhibiting
phosphorylation of Src, migration and invasion in the 4T1 cell line, as well as angiogenesis
treatment with dasatinib impaired the metastatic ability of tumor cells as assessed by a tail vein injection model. However, both the syngeneic BALB/c and the athymic nu/nu mice receiving oral doses of the drug developed significantly higher numbers of 4T1 lung metastases. This effect was neither seen in a different breast carcinoma cell line, the MDA-MB-231-4175-LM2 nor in the murine fibrosarcoma KHT cell line.
The 4T1 cell line is not an appropriate model to study Src inhibition.
[Mobile Full text]
Aberrant expression of p14
in human cancers: A new biomarker?
Kazushi Inoue, Elizabeth A Fry
April-June 2018, 1(2):37-44
genes are located on the same
locus, both showing its tumor-suppressive activity. ARF has been shown to monitor potentially harmful oncogenic signalings, making incipient cancer cells undergo senescence or programmed cell death to prevent cancer. On the other hand,
detects both aging and incipient cancer cell signals. The efficiency of detection of oncogenic signals is more efficient for the for the former than the latter in the mouse system. Both
genes are inactivated by gene deletion, promoter methylation, frameshift, aberrant splicing although point mutations for the coding region affect only the latter. Recent studies show the splicing alterations that affect only
genes, suggesting that
is inactivated in human tumors more frequently than what was previously thought. The
gene is activated by E2Fs and Dmp1 transcription factors while it is repressed by Bmi1, Tbx2/3, Twist1, and Pokemon nuclear proteins. It is also regulated at protein levels by Arf ubiquitin ligase named ULF, MKRN1, and Siva1. The prognostic value of ARF overexpression is controversial since it is induced in early-stage cancer cells to eliminate premalignant cells (better prognosis); however, it may also indicate that the tumor cells have mutant p53 associated with worse prognosis. The ARF tumor suppressive protein can be used as a biomarker to detect early-stage cancer cells as well as advanced stage tumors with p53 inactivation.
[Mobile Full text]
* Source: CrossRef
© Tumor and Microenvironment | Published by Wolters Kluwer -
Online since 18