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

Kimura, Shinya ; Ito, Chihiro ; Jyoko, Naoto ; Segawa, Hidekazu ; Kuroda, Junya ; Okada, Masayuki ; Adachi, Souichi ; Nakahata, Tatsutoshi ; Yuasa, Takeshi ; Filho, Valdir Cechinel ; Furukawa, Hiroshi ; Maekawa, Taira

International journal of cancer, 2005-01, Vol.113 (1), p.158-165 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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Título:
Inhibition of leukemic cell growth by a novel anti‐cancer drug (GUT‐70) from calophyllum brasiliense that acts by induction of apoptosis
Autor: Kimura, Shinya ; Ito, Chihiro ; Jyoko, Naoto ; Segawa, Hidekazu ; Kuroda, Junya ; Okada, Masayuki ; Adachi, Souichi ; Nakahata, Tatsutoshi ; Yuasa, Takeshi ; Filho, Valdir Cechinel ; Furukawa, Hiroshi ; Maekawa, Taira
Assuntos: Adenocarcinoma - drug therapy ; Antineoplastic Agents, Phytogenic - chemistry ; Antineoplastic Agents, Phytogenic - pharmacology ; apoptosis ; Apoptosis - drug effects ; Biological and medical sciences ; Brazil ; Calophyllum ; Calophyllum brasiliense ; caspase ; Caspases - drug effects ; Cell Line, Tumor ; Colorectal Neoplasms - drug therapy ; coumarin ; Coumarins - pharmacology ; Flow Cytometry ; Gene Expression Regulation, Neoplastic - drug effects ; General pharmacology ; Humans ; leukemia ; Leukemia - drug therapy ; Medical sciences ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Tumors
É parte de: International journal of cancer, 2005-01, Vol.113 (1), p.158-165
Notas: Fax: +81‐75‐751‐3631, +81‐75‐751‐4283
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Descrição: 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 (C23H26O5), inhibited all 6 human leukemic cell lines evaluated, including the P‐glycoprotein overexpressing cell line, in a concentration and time‐dependent manner with IC50 values from 2–5 μM. Furthermore, GUT‐70 did not inhibit colony formation by normal hematopoietic progenitors up to 30 μM and also did not inhibit the proliferation of normal human hepatocytes up to 30 μM. 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‐p2lWAFl/CIP1 pathway and increased the overall expression of p27KIP1 and p57KIP2, to stop the cell cycle at the G1/S transition. Thus, a novel anti‐cancer drug, GUT‐70 isolated from the stem bark of C. brasiliense induces caspase‐mediated and p53‐independent apoptosis to overcome multidrug resistance and may become a potent leukemia therapeutics.
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

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

Kimura, Shinya ; Ito, Chihiro ; Jyoko, Naoto ; Segawa, Hidekazu ; Kuroda, Junya ; Okada, Masayuki ; Adachi, Souichi ; Nakahata, Tatsutoshi ; Yuasa, Takeshi ; Filho, Valdir Cechinel ; Furukawa, Hiroshi ; Maekawa, Taira

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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