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Anticancer activity of methylene blue via inhibition of heat shock protein 70
- Source :
- Biomedicine & Pharmacotherapy. 107:1037-1045
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Introduction Heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) chaperones are indispensable to lung cancer cells for their survival and proliferation. In this study we evaluated and compared anticancer potential of methylene blue (MB) as an Hsp70 inhibitor, novobiocin (NB) a well-known Hsp90 inhibitor and their combination. Methods In vitro evaluation was done by cell viability assays, fluorescent staining, and flow cytometry analysis using A549 non-small cell lung cancer cells. In vivo anticancer activity was investigated by evaluating oxidative stress, tumor biomarkers, weight, lung microarchitecture, and Hsp70 and Hsp90 inhibitions via immunoblotting in benzo[a]pyrene induced lung carcinogenesis mice model. Results Using A549 NSCLC cells, we found MB demonstrated lower cell viability versus NB. Together, MB + NB resulted in further decrease in cell viability. SRB assay revealed significantly superior and similar potency for MB versus NB and MB + NB (1:1) versus MB, respectively. Fluorescent staining and flow cytometry analysis displayed early apoptosis by MB (11.4%); early and late apoptosis by MB + NB (13.8%). In vivo, MB significantly inhibited Hsp70. Furthermore, MB significantly alleviated tumor biomarkers (ADA and LDH) and improved lung histopathological features more than NB. Additionally, MB significantly improved SOD, not more than MB + NB or NB and improved LPO. Conclusion MB demonstrated potent anticancer activity in vitro and in vivo via inhibition of Hsp70 in benzo[a]pyrene induced lung carcinogenesis in mice.
- Subjects :
- Male
0301 basic medicine
Lung Neoplasms
Cell Survival
Apoptosis
Flow cytometry
Hsp90 inhibitor
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Carcinoma, Non-Small-Cell Lung
Heat shock protein
Antineoplastic Combined Chemotherapy Protocols
Benzo(a)pyrene
Biomarkers, Tumor
medicine
Animals
Humans
HSP70 Heat-Shock Proteins
HSP90 Heat-Shock Proteins
Viability assay
Cell Proliferation
Pharmacology
medicine.diagnostic_test
General Medicine
Flow Cytometry
Molecular biology
Hsp70
Methylene Blue
Oxidative Stress
030104 developmental biology
chemistry
A549 Cells
030220 oncology & carcinogenesis
Novobiocin
Subjects
Details
- ISSN :
- 07533322
- Volume :
- 107
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....2267c37265a9d63c25543ad0f4b6b51e