Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic Agents, in Colorectal Cancer Cells

Cancer Research and Treatment : Official Journal of Korean Cancer Association
Mi Hyun KangJee Hyun Kim

Abstract

HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in CRC cell lines. The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index. The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50, 0.003 µM and 0.005 µM, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells. These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, sing...Continue Reading

References

Nov 21, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J A McKayH L McLeod
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
May 3, 2005·Nature Reviews. Cancer·Nancy E Hynes, Heidi A Lane
Jul 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·Todd A CarterDavid J Lockhart
Dec 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mace L RothenbergRobert J Coffey
Oct 20, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heinz-Josef LenzEric K Rowinsky
Mar 17, 2007·ChemMedChem·Yovani Marrero-PonceRichard Rotondo
Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
Aug 1, 2008·Bioorganic & Medicinal Chemistry Letters·Wooyoung HurNathanael S Gray
Nov 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·George A FisherBranimir I Sikic
Oct 15, 2009·Anti-cancer Drugs·Helmout Modjtahedi, Sharadah Essapen
Jun 24, 2010·Cancer Research·Manickam JanakiramanDavid B Solit
Mar 15, 2011·Journal of the National Cancer Institute·Jeeyun LeeWon Ki Kang
Jul 7, 2011·International Journal of Cancer. Journal International Du Cancer·Mi Young ChaMaeng Sup Kim
Dec 23, 2011·Molecular Oncology·Rodrigo DienstmannJosep Tabernero
Dec 4, 2012·Recent Patents on Anti-cancer Drug Discovery·John S JarboeChristopher D Willey
Sep 18, 2013·Oncogenesis·D AhmedR A Lothe

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
fluorescence-activated cell sorting

Software Mentioned

Pro
CalcuSyn
CellQuest

Related Concepts

Related Feeds

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