Anticancer activity of methylene blue via inhibition of heat shock protein 70.

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.

Therapeutic Approaches for the Treatment of Epidermal Growth Factor Receptor Mutated Lung Cancer.

Lung cancer surfaces to be the predominant determinant of mortality worldwide constituting 13% and 19% of all new cancer cases and deaths related to cancer respectively. Molecular profiling has now become a regular trend in lung cancer to identify the driver mutations. Epidermal Growth Factor Receptor (EGFR) is the most regular driver mutation encountered in Non-Small Cell Lung Cancer (NSCLC). Targeted therapies are now available for the treatment of EGFR mutant NSCLC. EGFR mutation is more frequently expressed in adenocarcinoma than squamous cell carcinoma. This article presents a detailed molecular insight of the therapeutic approaches for the treatment of EGFR mutant lung cancer. The article delineates molecular mechanism of the drugs that are approved, the drugs that are in clinical trial and the drugs that have not entered a clinical trial but shows promising future in the treatment of EGFR mutant lung cancer. Furthermore, this article provides concise information on relevant combinational or monotherapy clinical trials that have been completed for various approaches.

Oncolytic Herpes Simplex Viral Therapy: A Stride toward Selective Targeting of Cancer Cells.

Oncolytic viral therapy, which makes use of replication-competent lytic viruses, has emerged as a promising modality to treat malignancies. It has shown meaningful outcomes in both solid tumor and hematologic malignancies. Advancements during the last decade, mainly genetic engineering of oncolytic viruses have resulted in improved specificity and efficacy of oncolytic viruses in cancer therapeutics. Oncolytic viral therapy for treating cancer with herpes simplex virus-1 has been of particular interest owing to its range of benefits like: (a) large genome and power to infiltrate in the tumor, (b) easy access to manipulation with the flexibility to insert multiple transgenes, (c) infecting majority of the malignant cell types with quick replication in the infected cells and (d) as Anti-HSV agent to terminate HSV replication. This review provides an exhaustive list of oncolytic herpes simplex virus-1 along with their genetic alterations. It also encompasses the major developments in oncolytic herpes simplex-1 viral therapy and outlines the limitations and drawbacks of oncolytic herpes simplex viral therapy.