Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells

Oncology Reports
Hyun Sook LimNam Deuk Kim

Abstract

The anticancer properties of MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, in various human cancer cell lines have been previously reported. The aim of the present study was to investigate the activities of MHY-449 on human lung cancer cells in order to elucidate its underlying molecular mechanisms of action. The result showed that MHY-449 treatment inhibited cell growth in a time- and concentration‑dependent manner. Specifically, MHY-449 induced cell cycle arrest at the S phase, and the resulting increased sub-G1 fraction led to the induction of apoptosis, as determined by flow cytometric analysis and DNA fragmentation. In addition, MHY-449 was shown to induce alterations in the ratio of Bax/Bcl-2 protein expression, and contribute to the loss of mitochondrial membrane potential. These cellular events then triggered the caspase cascade and subsequent poly(ADP‑ribose) polymerase cleavage. The apoptotic cell death induced by MHY-449 was inhibited by pretreatment with Z-VAD‑FMK, a pan-caspase inhibitor. Moreover, MHY-449 downregulated the phosphorylation of Akt, and the phosphatidylinositol-3 kinase/Akt inhibitor LY294002 was found to enhance its induction of apoptosis. Taken together, the results su...Continue Reading

References

Mar 15, 1997·Genes & Development·S G KennedyN Hay
Aug 13, 1999·Genes & Development·A GrossS J Korsmeyer
May 10, 2000·Nature Medicine·G Kroemer, J C Reed
Dec 6, 2000·Microbiology and Molecular Biology Reviews : MMBR·H Y Chang, X Yang
Jan 20, 2004·Molecular and Cellular Biology·Krishna Murthi VasudevanVivek M Rangnekar
Sep 30, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ramaswamy GovindanJay Piccirillo
Dec 13, 2007·Nature Reviews. Molecular Cell Biology·Rebecca C TaylorSeamus J Martin
Aug 5, 2010·Nature Reviews. Molecular Cell Biology·Stephen W G Tait, Douglas R Green
Feb 8, 2011·Biochimica Et Biophysica Acta·Chahrazade Kantari, Henning Walczak
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Sep 3, 2011·Bioorganic & Medicinal Chemistry Letters·Jin-Ah KangHyung Ryong Moon
Jun 25, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·M PuglisiU Banerji
Feb 18, 2015·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Saketh S DinavahiSrikant Viswanadha
Mar 13, 2015·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Kyu-Won JungKang Hyun Lee
Mar 18, 2015·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Kyu-Won JungKang Hyun Lee

❮ Previous
Next ❯

Citations

Dec 20, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Wan-Ting XuCheng-Hao Jin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis