RETRACTED ARTICLE: Quinoxaline 1,4-dioxides induce G2/M cell cycle arrest and apoptosis in human colon cancer cells
Authors: Makhluf J Haddadin
Hala U Gali-Muhtasib
Mona Diab-Assaf
Journal: Cancer Chemotherapy and Pharmacology (2005)
Discipline: CLINICAL MEDICINE
Keywords: quinoxaline 1,4-dioxide; T-84 human colon cancer cells; cell cycle arrest; apoptosis; cyclin B
Affiliations: Department of Biology, American University of Beirut, Beirut, Lebanon. ., Department of Biology, American University of Beirut, Beirut, Lebanon., Department of Chemistry, American University of Beirut, Beirut, Lebanon.

Abstract:  We have recently shown that quinoxaline 1,4-dioxide (QdNO) derivatives, namely 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide (DCQ), 2-benzoyl-3-phenyl-quinoxaline 1,4-dioxide (BPQ) and 2-acetyl-3-methyl-quinoxaline 1,4-dioxide (AMQ), suppress the growth of T-84 human colon cancer cells. Here we show that the growth-suppressive effects of QdNOs are due to their ability to induce cell cycle arrest and/or apoptosis. While AMQ blocked more than 60% of cells at the G2/M phase without inducing apoptosis, DCQ caused a significant increase in apoptotic cells with no noticeable effects on the cycling of cells. Treatment with BPQ resulted in G2/M cell cycle arrest and induction of apoptosis. With regard to the effects of QdNOs on molecules that regulate apoptosis and the G2 to M transition, both BPQ and AMQ inhibited the expression of cyclin B, while DCQ significantly decreased the levels of Bcl-2 and increased Bax expression. Next, we investigated whether transforming growth factor-beta1 (TGF-beta1) and/or extracellular signal-regulated kinase (ERK) mediate the antiproliferative and apoptotic effects of QdNOs in colon cancer cells. Interestingly, the above QdNOs increased differentially total TGF beta1 mRNA expression and decreased TGF alpha mRNA and ERK phosphorylation. None of these QdNOs induced changes in TGF beta-2 mRNA expression. The addition of a specific inhibitor of MEK greatly enhanced apoptosis in cells treated with DCQ, suggesting that the inhibition of ERK phosphorylation may explain, to an extent, the apoptogenic effects of this compound. Taken together, these findings provide insights into possible molecular mechanisms of growth inhibition by QdNOs that could aid in their evaluation for anticancer therapy. 

Retracted: Yes

PubPeer comments:
 March 2018 retraction notice.  The authors have retracted this article [1] because of overlap in images within the publication and with another previously published article [2]. It was brought to our attention that there are inconsistencies in Figs. 3, 5 and 6. The left middle panel in Fig. 3, labeled u201cCtrlu201d, is the same as the left panel in Fig. 6, labeled u201cPD98059u201d, except that the latter is flipped upside down and right-left. In Fig. 5, the gel in the middle left panel labeled TGF-u03b22 has been cropped in two different ways and used in Figs. 2 and 3 of Harakeh et al. [2]. This has been investigated by the Internal Research Integrity panel of the American University of Beirut who recommended retraction of the article as the original data are not available. *All authors agree to this retraction. Here is an illustration of the duplicated panel in Figures 3 and 6, marked with green boxes: ![file] , 
 Not mentioned in the Retraction Notice, but reported to the journal in June 2015, are potential concerns in Figure 4. Here is a copy of the report sent to the journal, with lanes that look similar marked with boxes of the same color. ![file] ,