2013
DOI: 10.1016/j.bcp.2013.09.022
|View full text |Cite
|
Sign up to set email alerts
|

Novel compound 1,3-bis (3,5-dichlorophenyl) urea inhibits lung cancer progression

Abstract: The successful clinical management of lung cancer is limited by frequent loss-of-function mutations in p53 which cooperates with chronic oxidant-stress induced adaptations in mercapturic acid pathway (MAP) which in turn regulates critical intracellular signaling cascades that determine therapeutic refractoriness. Hence, we investigated the anti-cancer effects and mechanisms of action of a novel compound called 1, 3 bis (3, 5-dichlorophenyl) urea (COH-SR4) in lung cancer. Treatment with COH-SR4 effectively inhi… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
4
1

Citation Types

4
4
0

Year Published

2015
2015
2022
2022

Publication Types

Select...
8

Relationship

2
6

Authors

Journals

citations
Cited by 9 publications
(8 citation statements)
references
References 44 publications
4
4
0
Order By: Relevance
“…These factors result in the assembly of the apoptosome and commitment of the cell to apoptosis. To our knowledge, this is the first study that confirms the potential of uncouplers as anticancer therapy, although we have previously shown SR4 to inhibit lung cancer and melanoma progression in xenograft animal models (31,32). Our results also suggest that SR4 is a useful probe for studying mitocan-based processes for the treatment as well as prevention of HCC through targeting critical cellular processes in its pathogenesis and progression.…”
Section: Discussionsupporting
confidence: 56%
See 1 more Smart Citation
“…These factors result in the assembly of the apoptosome and commitment of the cell to apoptosis. To our knowledge, this is the first study that confirms the potential of uncouplers as anticancer therapy, although we have previously shown SR4 to inhibit lung cancer and melanoma progression in xenograft animal models (31,32). Our results also suggest that SR4 is a useful probe for studying mitocan-based processes for the treatment as well as prevention of HCC through targeting critical cellular processes in its pathogenesis and progression.…”
Section: Discussionsupporting
confidence: 56%
“…This is a novel finding and helps to delineate how SR4 exerts potent anticancer effects in HCC. In a previously published study (31,32), we found that the oral administration of SR4 was well tolerated without any overt toxicity along with inducing effective tumor inhibition in both syngeneic and nude mouse xenograft models of melanoma and lung cancer. Thus, we believe that SR4 is a novel mitochondrial uncoupling agent that elicits desirable responses across multiple cancer types and warrants additional study to standardize dose, routes of administration, organ targeting, and bioavailability in humans.…”
Section: Discussionmentioning
confidence: 86%
“…Some of the reported detrimental effects of AMPK activation include increased food intake and body weight gain via activation of the hypothalamic AMPK. Both SR4 and niclosamide had no effect on body weight in the current study, consistent with the earlier observations in other xenograft experiments [26, 27, 31]. These suggest that the risk associated with the SR4 or niclosamide-induced mitochondria uncoupling is probably low.…”
Section: Discussionsupporting
confidence: 92%
“…In terms of cell signaling, the best-known effect of mitochondrial uncouplers is probably a drop in ATP/AMP levels, which induces the activation of the AMPK signaling pathway (Figure 1). This effect has been found in multiple models and species, including white adipocytes [91,251], skeletal muscle cells [252,253], cancer cells [54,254,255,256], and neurons [257]. In addition to AMPK activation (AMPKα1/α2 phosphorylation on Thr172), the mTOR-PI3K-MAPK axis is suppressed in response to mitochondrial uncoupling.…”
Section: Cellular Responses To Mitochondrial Uncouplingmentioning
confidence: 99%