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Open AccessArticle

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

1
Department of Biology, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
2
Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt
3
University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96822, USA
4
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; https://doi.org/10.3390/ijms16011544
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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