Crocin exerts anti-proliferative and apoptotic effects on cutaneous squamous cell carcinoma via miR-320a/ATG2B

Abstract

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent skin malignancy, and the effective therapy still remains a challenge. Crocin can be used for cSCC therapy. This study explored the effects of cSCC cells treatment with crocin in vitro and in vivo. The study used A431 and SCL-1 cells lines, cSCC human samples and BALB/C nude mice for investigations. Apoptosis was determined by MTT assays, while miR-320a and ATG2B expressions were validated through RT-qPCR. Interaction of miR-320a with ATG2B was examined via dual luciferase reporter assay. The autophagy and apoptosis proteins expressions were further confirmed through western blot and immunofluorescence staining assays. The results indicated a significantly upregulated miR-320a, but a down-regulated ATG2B expression in the cSCC clinical samples. Crocin significantly repressed cSCC cells growth, and induced apoptosis through autophagy. Furthermore, miR-320a expression was inhibited and ATG2B expression was increased. Dual luciferase reporter assay revealed that miR-320a regulated ATG2B expression directly. Additionally, the upregulation of ATG2B expression in cSCC cells inhibited cell proliferation and led to cell apoptosis. Crocin also reduced tumor growth and stimulated the apoptosis in vivo. In conclusion, miR-320a is upregulated and ATG2B is down-regulated in cSCC, Crocin suppresses the proliferation and induces apoptosis of cSCC cells. Further, Crocin increases autophagy while miR-320a hinders autophagy and the apoptotic effects of crocin on cSCC cells. MiR-320a binds ATG2B directly, and ATG2B expression is upregulated by crocin. Finally, Crocin triggers cSCC cells apoptosis in vivo. Crocin can target ATG2B/miR-320a and may be an effective alternative for cSCC treatment.

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights

“…Crocin was reported to play an important role in the regulation of angiogenesis pathways in breast cancer [ 70 ]. Various mechanisms for crocin to suppress cancer cell proliferation and induce apoptosis such as inhibition of key enzymes in nucleic acids synthesis, and remodification of epigenetic properties were suggested by [ 71 ]. In the present study, crocin apoptosis induction and growth arrest in HCC was confirmed.…”

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

“…Xuemei Zhang et al found that methylation of ATG2B CpG island promoter might be associated with the initiation and progression of breast carcinoma [41]. Xiaoqing Bi et al reported that upregulation of ATG2B could inhibit cell proliferation and lead to cell apoptosis in cutaneous squamous cell carcinoma cells [42]. There were also many reports indicating that ATG2B was associated with drug resistance by activating autophagy in multiple tumors [10,11].…”

The prognostic value of autophagy related genes with tumor- suppressor function in Ewing sarcoma

“…Xuemei Zhang et al found that methylation of ATG2B CpG island promoter might be associated with the initiation and progression of breast carcinoma (31). Xiaoqing Bi et al reported that upregulation of ATG2B could inhibit cell proliferation and lead to cell apoptosis in cutaneous squamous cell carcinoma cells (32). There were also many reports indicating that ATG2B was associated with drug resistance by activating autophagy in multiple tumors.…”