International Journal of Molecular Sciences | |
Defective Autophagosome Formation in p53-Null Colorectal Cancer Reinforces Crocin-Induced Apoptosis | |
Amr Amin1  Khuloud Bajbouj1  Adrian Koch2  Muktheshwar Gandesiri2  Regine Schneider-Stock2  | |
[1] Department of Biology, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates; E-Mail:;Experimental Tumor Pathology, Institute of Pathology, University of Erlangen, Erlangen 91054, Germany; E-Mails: | |
关键词: autophagy; autophagosome; apoptosis; crocin; colorectal cancer; p53; | |
DOI : 10.3390/ijms16011544 | |
来源: mdpi | |
【 摘 要 】
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.
【 授权许可】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
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