Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Int. J. Mol. Sci. 2013, 14(1), 850-870; doi:10.3390/ijms14010850
Article

Apoptosis is Induced in Cancer Cells via the Mitochondrial Pathway by the Novel Xylocydine-Derived Compound JRS-15

1
, 1
, 1
, 2
, 3
, 1
, 1
, 1
, 2,*  and 1,*
Received: 24 October 2012; in revised form: 17 December 2012 / Accepted: 21 December 2012 / Published: 4 January 2013
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
View Full-Text   |   Download PDF [4047 KB, uploaded 19 June 2014]
Abstract: The novel compound JRS-15 was obtained through the chemical modification of xylocydine. JRS-15 exhibited much stronger cytotoxic and pro-apoptotic activity than its parent compound in various cancer cell lines, with IC50 values in HeLa, HepG2, SK-HEP-1, PC-3M and A549 cells ranging from 12.42 to 28.25 µM. In addition, it is more potent for killing cancer than non-cancerous cells. Mechanistic studies showed that JRS-15 treatment arrested cell cycle at the G1/S phase, which further triggered the translocation of Bax and Bak to the mitochondria, resulting in mitochondrial membrane potential (MMP) depolarization and the subsequent release of cytochrome c and the second mitochondria-derived activator of caspase (Smac). The sequential activation of caspase-9 and caspase-3/7 and the cleavage of poly (ADP-ribose) polymerase (PARP) were observed following these mitochondrial events. Caspase-8, an initiator caspase that is required to activate the membrane receptor-mediated extrinsic apoptosis pathway was not activated in JRS-15-treated cells. Further analysis showed that the levels of the anti-apoptotic proteins Bcl-xL and XIAP were significantly reduced upon JRS-15 treatment. Furthermore, the caspase-9 inhibitor z-LEHD-fmk, the pan-caspase inhibitor z-VAD-fmk, and Bcl-xL or XIAP overexpression all effectively prevented JRS-15-induced apoptosis. Taken together, these results indicate that JRS-15 induces cancer cell apoptosis by regulating multiple apoptosis-related proteins, and this compound may therefore be a good candidate reagent for anticancer therapy.
Keywords: apoptosis; Bax; Bak; Bcl-xL; cell cycle; cytochrome c; JRS-15; Smac; XIAP apoptosis; Bax; Bak; Bcl-xL; cell cycle; cytochrome c; JRS-15; Smac; XIAP
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Sun, C.; Guo, X.-X.; Zhu, D.; Xiao, C.; Bai, X.; Li, Y.; Zhan, Z.; Li, X.-L.; Song, Z.-G.; Jin, Y.-H. Apoptosis is Induced in Cancer Cells via the Mitochondrial Pathway by the Novel Xylocydine-Derived Compound JRS-15. Int. J. Mol. Sci. 2013, 14, 850-870.

AMA Style

Sun C, Guo X-X, Zhu D, Xiao C, Bai X, Li Y, Zhan Z, Li X-L, Song Z-G, Jin Y-H. Apoptosis is Induced in Cancer Cells via the Mitochondrial Pathway by the Novel Xylocydine-Derived Compound JRS-15. International Journal of Molecular Sciences. 2013; 14(1):850-870.

Chicago/Turabian Style

Sun, Chao; Guo, Xiao-Xi; Zhu, Dan; Xiao, Chuan; Bai, Xiao; Li, Yang; Zhan, Zhuo; Li, Xiang-Long; Song, Zhi-Guang; Jin, Ying-Hua. 2013. "Apoptosis is Induced in Cancer Cells via the Mitochondrial Pathway by the Novel Xylocydine-Derived Compound JRS-15." Int. J. Mol. Sci. 14, no. 1: 850-870.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert