Abstract
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.
Highlights
Colorectal cancer (CRC) has the fourth most common malignant tumors worldwide [1]
Both cell lines showed the same pattern of reduced cell proliferation (65%) after 48 h of crocin treatment
Trypan blue staining was conducted for both cell lines treated with 10 mM crocin for 24 and 48 h
Summary
Colorectal cancer (CRC) has the fourth most common malignant tumors worldwide [1]. CRC mortality has been progressively declining since 1990, it still remains the second most common cause of cancer death in the US and Europe [2]. Europeans are diagnosed with CRC annually, and about one-third of those die of the disease [3]. Surgery is the primary treatment for colorectal cancer. Chemotherapy is used to reduce the likelihood of metastasis development, shrink tumor size, or slow tumor growth. Adjuvant chemotherapy has been recommended for stage III colon cancer patients [4]. The overall survival advantage in CRC patients treated with neoadjuvant therapy remains disappointing. In the new era of personalized cancer medicine, chemotherapy continues to be essential for treating patients with
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