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Open AccessArticle

Defective Autophagosome Formation in p53-Null Colorectal Cancer Reinforces Crocin-Induced Apoptosis

Department of Biology, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt
University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96822, USA
Experimental Tumor Pathology, Institute of Pathology, University of Erlangen, Erlangen 91054, Germany
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Rebecca L. Foster
Int. J. Mol. Sci. 2015, 16(1), 1544-1561;
Received: 28 October 2014 / Accepted: 22 December 2014 / Published: 9 January 2015
(This article belongs to the Section Biochemistry)
Crocin, a bioactive molecule of saffron, inhibited proliferation of both HCT116 wild-type and HCT116 p53−/− cell lines at a concentration of 10 mM. Flow cytometric analysis of cell cycle distribution revealed that there was an accumulation of HCT116 wild-type cells in G1 (55.9%, 56.1%) compared to the control (30.4%) after 24 and 48 h of crocin treatment, respectively. However, crocin induced only mild G2 arrest in HCT116 p53−/− after 24 h. Crocin induced inefficient autophagy in HCT116 p53−/− cells, where crocin induced the formation of LC3-II, which was combined with a decrease in the protein levels of Beclin 1 and Atg7 and no clear p62 degradation. Autophagosome formation was not detected in HCT116 p53−/− after crocin treatment predicting a nonfunctional autophagosome formation. There was a significant increase of p62 after treating the cells with Bafilomycin A1 (Baf) and crocin compared to crocin exposure alone. Annexin V staining showed that Baf-pretreatment enhanced the induction of apoptosis in HCT116 wild-type cells. Baf-exposed HCT116 p53−/− cells did not, however, show any enhancement of apoptosis induction despite an increase in the DNA damage-sensor accumulation, γH2AX indicating that crocin induced an autophagy-independent classical programmed cell death. View Full-Text
Keywords: autophagy; autophagosome; apoptosis; crocin; colorectal cancer; p53 autophagy; autophagosome; apoptosis; crocin; colorectal cancer; p53
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Amin, A.; Bajbouj, K.; Koch, A.; Gandesiri, M.; Schneider-Stock, R. Defective Autophagosome Formation in p53-Null Colorectal Cancer Reinforces Crocin-Induced Apoptosis. Int. J. Mol. Sci. 2015, 16, 1544-1561.

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