Combined Treatment with CCI779 and SB203580 Induces Cellular Senescence in Renal Cell Carcinoma Cell Line via p53 Pathway

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BACKGROUND: Renal cell carcinoma (RCC) is one of the most common neoplasms that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In recent years, there have been significant advancements implemented to understanding the biology of RCC, which has led to the introduction of novel targeted therapies in the management of patients with metastatic disease.

OBJECTIVE: The present study was designed to evaluate the effects of p38 MAPK inhibitor (SB203580), alone and in combination with mTOR inhibitor (CCI779) on apoptosis and cell proliferation.

METHOD: Subtoxic concentrations of inhibitors were selected by MTT assay using A-498, ACHN and primary culture of RCC.

RESULTS: All the three types of RCC cells had almost similar response towards these inhibitors. The results revealed that 25µM of SB203580 and 20µM of CCI779 at 48 hrs decreased cell viability by 20% and 30%, respectively, whereas the combination of both inhibitors showed a maximum of 40% reduction in cell viability.

CONCLUSION: The study concludes that the combination of SB203580 and CCI779 inhibitors may induce cellular senescence in A-498 cells with higher potency than that of individual inhibitors.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:17

Enthalten in:

Anti-cancer agents in medicinal chemistry - 17(2017), 11 vom: 24. Nov., Seite 1545-1554

Sprache:

Englisch

Beteiligte Personen:

Chauhan, Ashutosh [VerfasserIn]
Ojha, Rani [VerfasserIn]
Semwal, Deepak K [VerfasserIn]
Mishra, Satyendra P [VerfasserIn]
Semwal, Ruchi B [VerfasserIn]

Links:

Volltext

Themen:

624KN6GM2T
Antineoplastic Agents
Apoptosis
Autophagy
CCI779
EC 2.7.11.1
EC 2.7.11.24
Imidazoles
Journal Article
OU13V1EYWQ
P38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Pyridines
Renal cell carcinoma
SB 203580
SB203580
Senescence.
Sirolimus
TOR Serine-Threonine Kinases
Temsirolimus
Tumor Suppressor Protein p53
W36ZG6FT64

Anmerkungen:

Date Completed 25.12.2017

Date Revised 04.12.2021

published: Print

Citation Status MEDLINE

doi:

10.2174/1871520617666170213111002

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM269613498