Induction of apoptosis in human cancer cells by candidaspongiolide, a novel sponge polyketide.

Journal of the National Cancer Institute
Daniela TrisciuoglioGiovanni Melillo

Abstract

Candidaspongiolide (CAN), a novel polyketide from a marine sponge, is the active component of a mixture that was found to be potently cytotoxic in the National Cancer Institute's 60-cell-line screen. Effects of CAN on U251 glioma and HCT116 colorectal cancer cells and on normal fibroblasts were assessed using radiolabeling studies to measure protein synthesis, clonogenic assays to measure cell survival, flow cytometry of annexin V- and propidium iodide-stained cells to measure apoptosis, and western blots in the presence or absence of specific inhibitors to assess accumulation and phosphorylation of potential downstream target proteins. CAN inhibited protein synthesis and potently induced apoptosis in both U251 and HCT116 cells, the latter in part by a caspase 12-dependent pathway. For example, 25%-30% of U251 or HCT116 cells became apoptotic after 24 hours of treatment with 100 nM CAN. CAN also rapidly induced sustained phosphorylation of eukaryotic translation initiation factor-2 (eIF2)-alpha at Ser51 and of the translation elongation factor eEF2 at Thr56, which could contribute to its dose-dependent inhibition of protein synthesis. Stable expression of dominant-negative eIF2alpha was sufficient to prevent CAN-induced eIF2alp...Continue Reading

References

Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·S D DerB R Williams
Jul 8, 1998·European Journal of Biochemistry·M KleijnA A Thomas
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·S R Kimball
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·R JagusG N Barber
Jul 13, 2001·The Journal of Biological Chemistry·R V RaoD E Bredesen
Jul 18, 2002·Annals of the New York Academy of Sciences·Giampaolo Tortora, Fortunato Ciardiello
Sep 7, 2002·Molecular and Cellular Biology·Peichuan ZhangDouglas R Cavener
Oct 16, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jeffrey D LaskinDebra L Laskin
Mar 4, 2003·Nature Reviews. Cancer·Davide Ruggero, Pier Paolo Pandolfi
Mar 23, 2004·Annals of the New York Academy of Sciences·Eva SzegezdiAfshin Samali
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
Dec 16, 2004·Bioorganic & Medicinal Chemistry·Shinichi NishimuraNobuhiro Fusetani
Jan 22, 2005·Seminars in Cell & Developmental Biology·Christopher G Proud
Feb 4, 2005·Nature·Joel D Richter, Nahum Sonenberg
Jul 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Marie-Eve BordeleauJerry Pelletier
Dec 1, 2005·Molecular Cancer Research : MCR·Douglas E FeldmanAlbert C Koong
Mar 15, 2006·Nature Chemical Biology·Marie-Eve BordeleauJerry Pelletier
Jul 25, 2006·Cancer Biology & Therapy·Twan van den BeuckenBradly G Wouters
Dec 13, 2006·Microbiology and Molecular Biology Reviews : MMBR·M A GarcíaM Esteban
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Jun 15, 2007·Journal of Natural Products·Tamara L MeragelmanTawnya C McKee
Aug 19, 2007·Journal of the American Chemical Society·Amos B Smith, Dongjoo Lee
Nov 14, 2007·Methods in Enzymology·Constantinos KoumenisAlbert C Koong

❮ Previous
Next ❯

Citations

Nov 26, 2010·Apoptosis : an International Journal on Programmed Cell Death·Miaoxin LinZijian Guo
Mar 2, 2012·Organic Letters·Thomas E SmithMary E Daub
Apr 28, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Annamaria Rapisarda, Giovanni Melillo
Jan 1, 2011·ISRN Pharmaceutics·Agus TriantoJunichi Tanaka
Apr 24, 2013·Free Radical Biology & Medicine·Toshio Inoue, Yoshihiro Suzuki-Karasaki
Jul 28, 2016·Marine Drugs·Nadia RuoccoMaria Costantini
Oct 14, 2017·Marine Drugs·Cinzia CalcabriniCarmela Fimognari
Jan 11, 2018·Marine Drugs·Helena ĆetkovićMaja Herak Bosnar
Jan 10, 2019·Marine Drugs·Giuseppe ErcolanoAngela Ianaro
Jan 15, 2013·International Journal of Oncology·Mizuki TochigiYoshihiro Suzuki-Karasaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. 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