Abstract
Liphagal, isolated from the marine sponge Aka coralliphaga, exhibits phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitory activity and cytotoxic effects in human cancer cells. Siphonodictyal B, the biogenetic precursor of liphagal, also has PI3K inhibitory activity. However, its cytotoxic or antitumor activities have not been evaluated. In this study, we demonstrated that siphonodictyal B inhibits several kinases such as CDK4/6, CDK7, and PIM2 in addition to PI3K in vitro and that siphonodictyal B exhibits more potent cytotoxic effects than liphagal against human colon cancer cell lines. Furthermore, treatment with siphonodictyal B resulted in increased PARP cleavage, a larger sub-G1 fraction, and a larger annexin V-positive cell population, all of which are indicative of apoptosis induction. As a mechanism of apoptosis induction, we found that siphonodictyal B activates the p38 MAPK pathway, leading the upregulation of proapoptotic factors. Moreover, siphonodictyal B increased ROS levels, thus promoting p38 MAPK pathway activation. NAC, an ROS scavenger, almost completely reversed both the cytotoxic and p38 MAPK pathway-activating effects of siphonodictyal B. These results indicate that the p38 MAPK pathway might be involved...Continue Reading
References
Mar 25, 2000·British Journal of Cancer·R A Bras-GonçalvesM F Poupon
Mar 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John BoyerPatrick G Johnston
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Jan 18, 2006·Organic Letters·Frederic MarionRaymond J Andersen
May 17, 2007·Apoptosis : an International Journal on Programmed Cell Death·Paloma BragadoAlmudena Porras
May 30, 2009·Nature Reviews. Drug Discovery·Dunyaporn TrachoothamPeng Huang
Jul 25, 2009·Nature Reviews. Cancer·Jeffrey A Engelman
Mar 20, 2010·Current Drug Targets·Huanjie Yang, Q Ping Dou
Jan 5, 2011·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·C P HsuY C Chung
Jan 18, 2011·Journal of Proteome Research·Kim Y C FungLeah Cosgrove
Oct 5, 2011·World Journal of Hepatology·Roslin J Thoppil, Anupam Bishayee
Oct 25, 2012·Expert Opinion on Investigational Drugs·Min HuangYi-Tao Wang
Dec 5, 2012·PloS One·Yu-Lin LinAnn-Lii Cheng
Jan 3, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Daisuke KitagawaYasuyuki Kirii
Oct 22, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Josep TaberneroCarmen J Allegra
Jul 12, 2014·BioMed Research International·Mohamed HassanNoriaki Sakuragi
Oct 18, 2014·Molecular Cancer Therapeutics·Enrique RozengurtJames Sinnet-Smith
Dec 24, 2014·Nature Reviews. Cancer·Lauren M ThorpeJean J Zhao
Jan 15, 2015·Current Colorectal Cancer Reports·Sandeep Sreevalsan, Stephen Safe
Apr 1, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Samira GoldarBehzad Baradaran
Oct 27, 2015·Molecular Medicine Reports·Feng-Qi FangPei-Yao Yu
Jan 12, 2016·Therapeutic Advances in Medical Oncology·William A HammondKabir Mody
Feb 5, 2016·Science Bulletin·Lei YangXiao-Ya Chen
May 15, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K YamazakiI Hyodo
Aug 31, 2016·The Lancet Oncology·Sebastian StintzingUNKNOWN FIRE-3 investigators
Nov 5, 2016·Biochimica Et Biophysica Acta·Maureen Redza-Dutordoir, Diana A Averill-Bates
Feb 10, 2017·Scientific Reports·Mingyue LiClara Bik-San Lau
Aug 6, 2017·Cancer Treatment Reviews·Filip Janku
Citations
Jan 16, 2020·Journal of Clinical Medicine·Daniel Sur AlexandruIrimie
Mar 11, 2020·Pharmaceutics·Catarina Roma-RodriguesAlexandra R Fernandes
Apr 16, 2020·Cancers·Lizeth G Meza GuzmanSandra E Nicholson
Apr 25, 2020·Anti-cancer Agents in Medicinal Chemistry·Dan LuQiang Tang
Jan 4, 2021·Journal of Cancer Research and Clinical Oncology·Jiaen WeiZunnan Huang
Oct 11, 2020·Biochimica Et Biophysica Acta. General Subjects·Gan QiaoXiukun Lin