Inhibition of leukemic cell growth by a novel anti-cancer drug (GUT-70) from calophyllum brasiliense that acts by induction of apoptosis

International Journal of Cancer. Journal International Du Cancer
Shinya KimuraTaira Maekawa

Abstract

During our search for cancer chemopreventing compounds derived from plant sources, we discovered that the natural product GUT-70, isolated from the stem bark of Calophyllum brasiliense collected in Brazil, significantly inhibits the growth of leukemic cells. GUT-70, characterized as a tricyclic coumarin, 5-methoxy-2,2-dimethyl-6-(2-methyl-1-oxo-2-butenyl) -10-propyl-2H,8H-benzo[1,2-b;3,4-b']dipyran-8-one (C(23)H(26)O(5)), inhibited all 6 human leukemic cell lines evaluated, including the P-glycoprotein overexpressing cell line, in a concentration and time-dependent manner with IC(50) values from 2-5 microM. Furthermore, GUT-70 did not inhibit colony formation by normal hematopoietic progenitors up to 30 microM and also did not inhibit the proliferation of normal human hepatocytes up to 30 microM. GUT-70 activated the caspase 2, 3, 8 and 9, and induced the apoptosis in leukemic cells, which was inhibited by caspase inhibitors. GUT-70 induced anti-leukemic effects independent of the p53-p2l(WAFl/CIP1) pathway and increased the overall expression of p27(KIP1) and p57(KIP2), to stop the cell cycle at the G(1)/S transition. Thus, a novel anti-cancer drug, GUT-70 isolated from the stem bark of C. brasiliense induces caspase-mediated ...Continue Reading

References

Mar 1, 1968·Tetrahedron Letters·K KawazuT Mitsui
Apr 1, 1967·Tetrahedron·T R GovindachariM Srinivasan
Aug 1, 1997·Trends in Biochemical Sciences·D W Nicholson, N A Thornberry
Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Nov 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D M Bradshaw, R J Arceci
Feb 6, 1999·Bioorganic & Medicinal Chemistry Letters·C SpinoS Sotheeswaran
Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Jul 10, 1999·The Journal of Biological Chemistry·B B Wolf, D R Green
Aug 5, 2000·Experimental & Molecular Medicine·J Y ShinJ Y Lee
Aug 17, 2000·British Journal of Cancer·M Oya, W A Schulz
Feb 24, 2001·Phytochemistry·A KijjoaW Herz
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Sep 28, 2001·Oncology·Y ItoN Matsuura
May 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Malcolm RansonEric K Rowinsky
May 17, 2002·Blood·David MasonHeddy Zola
Aug 15, 2002·Biochemical and Biophysical Research Communications·Magnus K R SamuelssonSam Okret
Aug 1, 1994·The New Phytologist·Richard N Bennett, Roger M Wallsgrove

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Citations

May 26, 2007·The Journal of Pharmacy and Pharmacology·César Ruiz-MarcialLourdes Rodríguez-Fragoso
Jun 30, 2006·The Journal of Pharmacy and Pharmacology·Chihiro ItoHiroshi Furukawa
Mar 29, 2014·The Journal of Pharmacy and Pharmacology·Juan C Gomez-VerjanRicardo Reyes-Chilpa
Jan 13, 2015·Biochemical and Biophysical Research Communications·Kouki MatsudaSeiji Okada
Feb 17, 2015·Journal of Advanced Research·Hossam M AbdallahAli M El-Halawany
Jun 28, 2011·Chemistry & Biology·Makoto KawataniHiroyuki Osada
Mar 5, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Jun YuWei Wei
Jun 8, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saikat DewanjeeMuhammad Zia-Ul-Haq
Dec 18, 2008·Chemistry & Biodiversity·Xiao-Hui SuQing-Wen Shi
Mar 26, 2009·Chemistry & Biodiversity·Valdir Cechinel FilhoRivaldo Niero
Mar 28, 2006·Journal of Natural Products·Gordon M CraggStringner S Yang

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