Author(s): Lu, HF (Lu, Hsu-Feng); Wang, HL (Wang, Hai-Lung); Chuang, YY (Chuang, Ying- Ying); Tang, YJ (Tang, Yih-Jing); Yang, JS (Yang, Jai-Sing); Ma, YS (Ma, Yi-Shih); Chiang, JH (Chiang, Jo-Hua); Lu, CC (Lu, Chi-Cheng); Yang, JL (Yang, Jiun-Long); Lai, TY (Lai, Tung- Yuan); Wu, CC (Wu, Chih-Chung); Chung, JG (Chung, Jing-Gung)
Title: Danthron Induced Apoptosis Through Mitochondria- and Caspase-3-Dependent Pathways in Human Brain Glioblastoma Multiforms GBM 8401 Cells
Source: NEUROCHEMICAL RESEARCH, 35 (3): 390-398 MAR 2010 Language: English
Document Type: Article
Author Keywords: Danthron; Apoptosis; Mitochondria; Caspase-3; GBM 8401 cells KeyWords Plus: ENDOPLASMIC-RETICULUM STRESS; BAICALEIN-INDUCED
APOPTOSIS; CA SKI CELLS; DEPENDENT PATHWAY; SIGNALING PATHWAY; CANCER- CELLS; G2/M ARREST; INDUCTION; EMODIN; DEATH
Abstract: Danthron (1,8-dihydroxyanthraquinone), is one of component from Rheum
palmatum L. (Polygonaceae), has been shown several biological activities but did not show to induce apoptosis in human brain tumor cells. The aim of this study is to investigate the mechanisms by danthron for the induction of apoptotic potential on human brain glioblastoma multiforms GBM 8401 cell line. Danthron showed a marked concentration- and time-
dependent inhibition of GBM 8401 cell viability and induced apoptosis in a dose-and time- dependent manner. There was an attenuation of mitochondrial membrane potential (Delta I (m) ) with the alterations of Bcl-2/Bax protein ratio in GBM 8401 cells, indicating the
participation of a mitochondria-related mechanism. Pretreatment of a caspase-8 inhibitor (Z- IETD-FMK), caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVE-FMK) significantly increased the viable of GBM 8401 cells implied that the participations of caspases. Western blotting analysis also showed the activation of initiator caspase-8 and caspase-9, and executor caspase-3 in GBM 8401 cells. Meanwhile, danthron also promoted the generation of reactive oxygen species (ROS) and cytosolic Ca2+ in GBM 8401 cells.
Taken together, our data showed that danthron induced apoptosis in GBM 8401 cells through mitochondria-related and caspase-related pathways, and it may be further evaluated as a chemotherapeutic agent for human brain cancer.
Addresses: [Chung, Jing-Gung] China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan; [Lu, Hsu-Feng] Cheng Hsin Rehabil Med Ctr, Dept Clin Pathol, Taipei, Taiwan; [Lu, Hsu-Feng] Fu Jen Catholic Univ, Coll Human Ecol, Taipei, Taiwan; [Wang, Hai-Lung; Chuang, Ying-Ying] Yuanpei Univ, Res Inst, Med Lab Sci & Biotechnol, Hsinchu, Taiwan; [Tang, Yih- Jing] Taichung Vet Gen Hosp, Dept Family Med, Taichung, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan; [Ma, Yi-Shih] China Med Univ, Grad Inst Chinese Med Sci, Taichung 404, Taiwan; [Ma, Yi-Shih] Chang Hua Hosp, Dept Chinese Med,
Changhua, Taiwan; [Chiang, Jo-Hua; Lu, Chi-Cheng] Natl Chung Hsing Univ, Dept Life Sci, Taichung 40227, Taiwan; [Yang, Jiun-Long] China Med Univ, Sch Chinese Pharmaceut Sci, Taichung 404, Taiwan; [Lai, Tung-Yuan] China Med Univ Hosp, Dept Chinese Internal Med, Taichung, Taiwan; [Lai, Tung-Yuan] China Med Univ, Sch Postbaccalaureate Chinese Med, Taichung 404, Taiwan; [Wu, Chih-Chung] Chang Jung Christian Univ, Dept Nutr & Hlth Sci, Tainan, Taiwan; [Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Taichung, Taiwan
Reprint Address: Chung, JG, China Med Univ, Dept Biol Sci & Technol, 91 Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected] Funding Acknowledgement:
Funding Agency Grant Number
China Medical University, Taichung, Taiwan CMU95-075
This work was supported by Grant CMU95-075 from China Medical University, Taichung, Taiwan.
Cited References: ASHKENAZI A, 2008, CYTOKINE GROWTH F R, V19, P325, DOI 10.1016/j.cytogfr.2008.04.001.
CHEN HC, 2004, FOOD CHEM TOXICOL, V42, P1251, DOI 10.1016/j.fct.2004.03.002.
CHIANG LC, 2006, CANCER LETT, V237, P207, DOI 10.1016/j.canlet.2005.06.002.
CHUNG JG, 2001, CANCER RES, V61, P8873.
FULDA S, 2006, ONCOGENE, V25, P4798, DOI 10.1038/sj.onc.1209608.
GALLUZZI L, 2007, APOPTOSIS, V12, P803, DOI 10.1007/s10495-007-0720-1.
GHOBRIAL IM, 2005, CA-CANCER J CLIN, V55, P178.
GIRI A, 2000, CYTOTECHNOLOGY, V34, P17.
HE DX, 2009, J PHARMACEUT BIOMED, V49, P1123, DOI 10.1016/j.jpba.2009.02.014.
HUANG AC, 2007, ANTICANCER RES, V27, P2505.
HUANG Q, 2007, MED RES REV, V27, P609, DOI 10.1002/med.20094.
HUANG ZW, 2008, ARCH PHARM RES, V31, P742, DOI 10.1007/s12272-001-1221-6.
IP SW, 2007, ANTICANCER RES, V27, P379.
JIN ZY, 2005, CANCER BIOL THER, V4, P139.
KWON YS, 2004, BIOL PHARM BULL, V27, P723.
LEE JH, 2008, ANTICANCER RES, V28, P1701.
LEE SH, 2008, CANCER LETT, V259, P39, DOI 10.1016/j.canlet.2007.09.015.
LI YC, 2009, NEUROCHEM RES, V34, P418, DOI 10.1007/s11064-008-9799-1.
LIN JG, 2006, J UROLOGY, V175, P343, DOI 10.1016/S0022-5347(05)00005-4.
LIN ML, 2007, ANTICANCER RES, V27, P3313.
LIN SS, 2008, CANCER LETT, V272, P77, DOI 10.1016/j.canlet.2008.06.031.
LIN YT, 2008, ANTICANCER RES, V28, P2791.
LU HF, 2009, NEUROCHEM RES, V34, P1575, DOI 10.1007/s11064-009-9946-3.
PACKARD BZ, 1996, P NATL ACAD SCI USA, V93, P11640.
PUTCHA GV, 2002, J CELL BIOL, V157, P441.
SAELENS X, 2004, ONCOGENE, V23, P2861, DOI 10.1038/sj.onc.1207523.
WAJANT H, 2002, SCIENCE, V296, P1635.
WALKER NI, 1988, AM J PATHOL, V131, P465.
WANG DY, 2002, NEUROCHEM RES, V27, P883.
WEI MC, 2000, GENE DEV, V14, P2060.
WENG JK, 2008, P NATL ACAD SCI USA, V105, P7887, DOI 10.1073/pnas.0801696105.
YANG JH, 2006, DRUG METAB DISPOS, V34, P296, DOI 10.1124/dmd.105.005280.
YANG JS, 2004, ANTICANCER RES, V24, P1769.
YANG JS, 2009, FOOD CHEM TOXICOL, V47, P171, DOI 10.1016/j.fct.2008.10.032.
ZAPATA JM, 2001, J BIOL CHEM, V276, P24242.
Cited Reference Count: 35 Times Cited: 0
Publisher: SPRINGER/PLENUM PUBLISHERS
Publisher Address: 233 SPRING ST, NEW YORK, NY 10013 USA ISSN: 0364-3190
DOI: 10.1007/s11064-009-0067-9
29-char Source Abbrev.: NEUROCHEM RES ISO Source Abbrev.: Neurochem. Res.
Source Item Page Count: 9
Subject Category: Biochemistry & Molecular Biology; Neurosciences ISI Document Delivery No.: 553YV
