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Cruz PG, Fribley AM, Miller JR, et al. Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts. ACS Med Chem Lett. 2015;6(8):877-81doi: 10.1021/acsmedchemlett.5b00127.
Cruz, P. G., Fribley, A. M., Miller, J. R., Larsen, M. J., Schultz, P. J., Jacob, R. T., Tamayo-Castillo, G., Kaufman, R. J., & Sherman, D. H. (2015). Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts. ACS medicinal chemistry letters, 6(8), 877-81. https://doi.org/10.1021/acsmedchemlett.5b00127
Cruz, Patricia G, et al. "Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts." ACS medicinal chemistry letters vol. 6,8 (2015): 877-81. doi: https://doi.org/10.1021/acsmedchemlett.5b00127
Cruz PG, Fribley AM, Miller JR, Larsen MJ, Schultz PJ, Jacob RT, Tamayo-Castillo G, Kaufman RJ, Sherman DH. Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts. ACS Med Chem Lett. 2015 Jul 06;6(8):877-81. doi: 10.1021/acsmedchemlett.5b00127. eCollection 2015 Aug 13. PMID: 26288688; PMCID: PMC4538430.
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ACS Med Chem Lett. 2015 Jul 06;6(8):877-81. doi: 10.1021/acsmedchemlett.5b00127. eCollection 2015 Aug 13.

Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts.

ACS medicinal chemistry letters

Patricia G Cruz, Andrew M Fribley, Justin R Miller, Martha J Larsen, Pamela J Schultz, Renju T Jacob, Giselle Tamayo-Castillo, Randal J Kaufman, David H Sherman

Affiliations

  1. Center for Chemical Genomics, Life Sciences Institute and Departments of Medicinal Chemistry, Chemistry, Microbiology & Immunology, University of Michigan , Ann Arbor, Michigan 48109-2216, United States.
  2. Carmen and Ann Adams Department of Pediatrics, Division of Hematology and Oncology, and the Karmanos Cancer Institute Molecular Therapeutics Program, Wayne State University , 2228 Elliman Building, 421 East Canfield, Detroit, Michigan 48201, United States.
  3. Instituto Nacional de Biodiversidad (INBio), Heredia, Costa Rica & CIPRONA-Escuela de Química, Universidad de Costa Rica (UCR) , 2061-San José, Costa Rica.
  4. Degenerative Disease Research Program, Center for Cancer Research, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States.

PMID: 26288688 PMCID: PMC4538430 DOI: 10.1021/acsmedchemlett.5b00127

Abstract

As part of the International Cooperative Biodiversity Groups (ICBG) Program, we were interested in identifying biologically active unfolded protein response (UPR) inducing compounds from marine microorganisms isolated from Costa Rican biota. With this aim in mind we have now generated more than 33,000 unique prefractionated natural product extracts from marine and terrestrial organisms that have been submitted to the Center of Chemical Genomics (CCG) at the University of Michigan for high throughput screening (HTS). An effective complementary cell-based assay to identify novel modulators of UPR signaling was used for screening extracts. Active fractions were iteratively subjected to reverse-phase HPLC chromatographic analysis, and together with lobophorin A, B, E, and F (1-4), three new lobophorin congeners, designated as CR1 (5), CR2 (6), and CR3 (7) were isolated. Herein, we report that secondary assays revealed that the new lobophorins induced UPR-associated gene expression, inhibited oral squamous cell carcinoma cell growth, and led to UPR-dependent cell death in murine embryonic fibroblast (MEF) cells.

Keywords: ATF4; CHOP; ER stress; UPR; anticancer; lobophorin; natural products; oral cancer; oral squamous cell carcinoma

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