American Association for Cancer Research
15357163mct130486-sup-fig_1.pdf (635.12 kB)

Supplementary Figure 1 from The Cannabinoid WIN 55,212-2 Decreases Specificity Protein Transcription Factors and the Oncogenic Cap Protein eIF4E in Colon Cancer Cells

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journal contribution
posted on 2023-04-03, 13:47 authored by Sandeep Sreevalsan, Stephen Safe

PDF - 635KB, Inhibition of CCD-18Co growth (A) and PP2A mediated effects of WIN on Sp proteins and ZBTB10 expression in RKO cells (B - E).



2,3-Dihydro-5-methyl-3-([morpholinyl]methyl)pyrollo(1,2,3-de)-1,4-benzoxazinyl]-[1-naphthaleny]methanone [WIN 55,212-2, (WIN)] is a synthetic cannabinoid that inhibits RKO, HT-29, and SW480 cell growth, induced apoptosis, and downregulated expression of survivin, cyclin D1, EGF receptor (EGFR), VEGF, and its receptor (VEGFR1). WIN also decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4, and this is consistent with the observed downregulation of the aforementioned Sp-regulated genes. In addition, we also observed by RNA interference (RNAi) that the oncogenic cap protein eIF4E was an Sp-regulated gene also downregulated by WIN in colon cancer cells. WIN-mediated repression of Sp proteins was not affected by cannabinoid receptor antagonists or by knockdown of the receptor but was attenuated by the phosphatase inhibitor sodium orthovanadate or by knockdown of protein phosphatase 2A (PP2A). WIN-mediated repression of Sp1, Sp3, and Sp4 was due to PP2A-dependent downregulation of microRNA-27a (miR-27a) and induction of miR-27a–regulated ZBTB10, which has previously been characterized as an “Sp repressor.” The results show that the anticancer activity of WIN is due, in part, to PP2A-dependent disruption of miR-27a:ZBTB10 and ZBTB10-mediated repression of Sp transcription factors and Sp-regulated genes, including eIF4E. Mol Cancer Ther; 12(11); 2483–93. ©2013 AACR.