The pterocarpanquinone LQB-118 inhibits tumor cell proliferation by downregulation of c-Myc and cyclins D1 and B1 mRNA and upregulation of p21 cell cycle inhibitor expression

• Published in: Bioorganic & medicinal chemistry Vol. 22; no. 12; pp. 3115 - 3122
• Main Authors: Martino, Thiago, Magalhães, Fernanda C.J., Justo, Graça A., Coelho, Marsen G.P., Netto, Chaquip D., Costa, Paulo R.R., Sabino, Kátia C.C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-06-2014
• Subjects: Apoptosis; Apoptosis - drug effects; c-Myc; Cell cycle; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cyclin D1 - antagonists & inhibitors; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - antagonists & inhibitors; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cyclins; Down-Regulation; Flow Cytometry; Gene Expression Regulation, Neoplastic - drug effects; Humans; LQB-118; Male; Naphthoquinones - pharmacology; PC3 cells; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-myc - antagonists & inhibitors; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Pterocarpans - pharmacology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Tumor Cells, Cultured; LQB-118; c-Myc; PC3 cells; Cyclins; Cell cycle; Apoptosis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.04.025

The incidence of cancer grows annually worldwide and in Brazil it is the second cause of death. The search for anti-cancer drugs has then become urgent. It depends on the studies of natural and chemical synthesis products. The antitumor action of LQB-118, a pterocarpanquinone structurally related to lapachol, has been demonstrated to induce mechanisms linked to leukemia cell apoptosis. This work investigated some mechanisms of the in vitro antitumor action of LQB-118 on prostate cancer cells. LQB-118 reduced the expression of the c-Myc transcription factor, downregulated the cyclin D1 and cyclin B1 mRNA levels and upregulated the p21 cell cycle inhibitor. These effects resulted in cell cycle arrest in the S and G2/M phases and inhibition of tumor cell proliferation. LQB-118 also induced programmed cell death of the prostate cancer cells, as evidenced by internucleosomal DNA fragmentation and annexin-V positive cells. Except the cell cycle arrest in the S phase and enhanced c-Myc expression, all the mechanisms observed here for the in vitro antitumor action of LQB-118 were also found for Paclitaxel, a traditional antineoplastic drug. These findings suggest new molecular mechanisms for the LQB-118 in vitro antitumor action.