The Cancer Stem Cell Inhibitor Napabucasin (BBI608) Shows General Cytotoxicity in Biliary Tract Cancer Cells and Reduces Cancer Stem Cell Characteristics

Cancers
Marlena BeyreisChristian Mayr

Abstract

Biliary tract cancer is a devastating disease with limited therapeutic options. The involvement of cancer stem cells in biliary tract cancer is likely. Napabucasin is a previously described cancer stem cell inhibitor that is currently being used in clinical trials. However, data regarding napabucasin and biliary tract cancer are not available yet. We tested the general cytotoxic effect of napabucasin on a comprehensive biliary tract cancer in vitro model, using resazurin assay and Annexin V/7-AAD staining. The effect of napabucasin on functional cancer stem cell characteristics was analyzed via soft agar assay, aldehyde-dehydrogenase-1 assay, measurement of surface CD326 expression, and measurement of clonogenic growth. The evaluation of the effect of napabucasin on cancer stem cell protein and gene expression was performed using Western blot and reverse transcription-PCR-based human cancer stem cell array. Napabucasin showed a concentration- and cell line-dependent cytotoxic effect, and increased the apoptotic and necrotic cell fractions. Treatment with napabucasin significantly reduced the formation of tumor spheres and clonogenic growth, as well as CD326 surface expression. Expression of cancer stem cell markers were reduced...Continue Reading

References

Jun 1, 1989·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·M MiyagiwaH Sasaki
Sep 1, 1981·British Journal of Cancer·R N Buick, W J MacKillop
Aug 13, 2002·Cancer Biology & Therapy·Jens Hasskarl, Karl Münger
Aug 15, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jun TangKimberly E Foreman
Jul 22, 2005·Nature Reviews. Cancer·Jonathan PerkRobert Benezra
Jun 25, 2008·Stem Cells and Development·Julie DouvilleDanuta Balicki
Jun 27, 2009·BMC Cancer·Emmanuelle Charafe-JauffretDaniel Birnbaum
Apr 2, 2010·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Tobias KiesslichFrieder Berr
Mar 30, 2011·Journal of Visualized Experiments : JoVE·Haloom RafehiTom C Karagiannis
May 23, 2012·International Journal of Oncology·Ralf KemmerlingTobias Kiesslich
Oct 2, 2013·Annals of Surgical Oncology·Anthony T RuysThomas M van Gulik
Dec 20, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J W ValleT Okusaka
Jan 11, 2014·World Journal of Gastroenterology : WJG·Jan HarderJens Hasskarl
Mar 4, 2014·Lancet·Nataliya Razumilava, Gregory J Gores
Mar 13, 2014·Cell Stem Cell·Antonija Kreso, John E Dick
Mar 29, 2014·Trends in Molecular Medicine·Sritama Nath, Pinku Mukherjee
Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Youzhi LiChiang J Li
Feb 6, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tsunekazu Oikawa
Feb 22, 2016·Stem Cell Research·Martin MüllerLukas Perkhofer
Oct 22, 2016·BMC Cancer·Sara S FrancoAndrás Dinnyés
Jan 25, 2017·Cancer·Tanios Bekaii-Saab, Bassel El-Rayes
May 4, 2017·World Journal of Gastroenterology : WJG·Christian MayrTobias Kiesslich
Jun 3, 2017·Drugs·Joleen M Hubbard, Axel Grothey
Aug 22, 2017·Therapeutic Advances in Respiratory Disease·Yanling XuJie Zhang
Mar 8, 2018·International Journal of Molecular Sciences·Christian MayrTobias Kiesslich
Apr 14, 2018·Cancer Letters·Lauren MacDonaghMartin P Barr
Jun 13, 2018·Japanese Journal of Clinical Oncology·Chigusa MorizaneJunji Furuse
Jun 26, 2018·Clinica Chimica Acta; International Journal of Clinical Chemistry·Miaomei YuGuanghua Luo
Oct 6, 2018·Journal of Experimental & Clinical Cancer Research : CR·Dongqing ZuoAvudaiappan Maran
Dec 2, 2018·Stem Cell Investigation·Fouad Saeg, Muralidharan Anbalagan
Dec 6, 2018·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Ah-Rong NamYung-Jue Bang

❮ Previous
Next ❯

Citations

May 30, 2020·International Journal of Oncology·Nicole A McgrathChangqing Xie
Aug 10, 2019·World Journal of Stem Cells·Fang-Yu DuGuo-Liang Chen
Aug 2, 2019·Cancer Cell International·Fei ZhouXiaoming Yang
Aug 11, 2020·Cancer Cell International·Silvia SchmidtovaLeendert H J Looijenga
Apr 26, 2020·Journal of Clinical Medicine·Dino BekricChristian Mayr
Jul 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jong Woo ParkJeung-Whan Han
Dec 22, 2020·Frontiers in Pharmacology·Ya LiJian Zhang
Dec 19, 2020·Frontiers in Oncology·Antons MartincuksLorna Rodriguez-Rodriguez

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
light microscopy
Assay
PCR

Software Mentioned

Kaluza Analysis
ImageJ
OriginPro

Related Concepts

Related Feeds

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

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.