Securin enhances the anti-cancer effects of 6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole (BPR0L075) in human colorectal cancer cells.

PloS One
Ho-Hsing TsengShu-Jun Chiu

Abstract

BPR0L075 [6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole] is a novel anti-microtubule drug with anti-tumor and anti-angiogenic activities in vitro and in vivo. Securin is required for genome stability, and is expressed abundantly in most cancer cells, promoting cell proliferation and tumorigenesis. In this study, we found that BPR0L075 efficiently induced cell death of HCT116 human colorectal cancer cells that have higher expression levels of securin. The cytotoxicity of BPR0L075 was attenuated in isogenic securin-null HCT116 cells. BPR0L075 induced DNA damage response, G(2)/M arrest, and activation of the spindle assembly checkpoint in HCT116 cells. Interestingly, BPR0L075 induced phosphorylation of securin. BPR0L075 withdrawal resulted in degradation of securin, mitotic exit, and mitotic catastrophe, which were attenuated in securin-null cells. Inhibition of cdc2 decreased securin phosphorylation, G(2)/M arrest and cell death induced by BPR0L075. Moreover, BPR0L075 caused cell death through a caspase-independent mechanism and activation of JNK and p38 MAPK pathways. These findings provided evidence for the first time that BPR0L075 treatment is beneficial for the treatment of human colorectal tumors with higher levels of ...Continue Reading

References

Apr 1, 1997·Molecular Endocrinology·L Pei, S Melmed
Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Apr 8, 2000·Current Opinion in Structural Biology·L A Amos
Sep 7, 2001·Genes & Development·R T Abraham
Dec 19, 2001·Cell·O StemmannM W Kirschner
May 7, 2002·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·I B RoninsonB D Chang
Oct 31, 2002·The Journal of Biological Chemistry·Yunli ZhouXun Zhang
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhiyong WangShlomo Melmed
Mar 17, 2004·Molecular and Cellular Biology·Francisco RomeroMaría Tortolero
Apr 23, 2005·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Selam OgbagabrielAnthony P Heaney
Oct 18, 2005·Molecular Cancer Therapeutics·David L MorseRobert J Gillies
Apr 22, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tsutomu FujiiAkimasa Nakao
May 10, 2006·Trends in Cell Biology·Christina Karlsson-Rosenthal, Jonathan B A Millar
May 18, 2006·Molecular and Cellular Biology·Ana M Gil-BernabéMaría Tortolero
Jul 1, 2006·Clinical Medicine & Research·Jacob Tfelt-HansenNaibedya Chattopadhyay
Feb 28, 2007·Endocrine Reviews·George VlotidesShlomo Melmed
Mar 14, 2007·Anti-cancer Agents in Medicinal Chemistry·Alex KiselyovAlexandre V Ivachtchenko
Apr 12, 2008·Cell Death and Differentiation·H VakifahmetogluB Zhivotovsky
Sep 17, 2008·Molecular and Cellular Biology·Yan-Nian LiuJi-Hshiung Chen
Nov 20, 2008·Cancer Science·Yoshiyuki KimuraKimiye Baba
May 13, 2009·Journal of Molecular Endocrinology·Yunguang Tong, Tamar Eigler
Jun 11, 2009·Molecular Cancer Therapeutics·Michael E BekierWilliam R Taylor
May 12, 2010·International Journal of Radiation Oncology, Biology, Physics·Wen-Shu ChenShu-Jun Chiu
May 28, 2010·Journal of Cellular Biochemistry·Ren-Huei JiangJui-I Chao
Oct 5, 2010·Nature Reviews. Drug Discovery·Charles Dumontet, Mary Ann Jordan
Apr 30, 2011·Nature Reviews. Molecular Cell Biology·Ilio VitaleGuido Kroemer

❮ Previous
Next ❯

Citations

May 30, 2014·The American Journal of Chinese Medicine·Shin-Hwar WuJing-Gung Chung
Nov 26, 2015·Bioorganic & Medicinal Chemistry·Vandana Srivastava, Hoyun Lee
Mar 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chaochao GeChaojie Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
electrophoresis
X-ray

Software Mentioned

- Scan - It gel
GraphPad Prism
ModFit LT
Un

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

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

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.