Melittin treatment prevents colorectal cancer from progressing in mice through ER stress-mediated apoptosis

Melittin treatment inhibits CRC progression by inducing ER stress and an imbalance in calcium homeostasis.

The viability of cancer cells was tested using the MTT assay, and the apoptosis of tumour cells was assayed using Annexin V/PI staining in vitro or TUNEL staining in vivo. The in vivo toxicity and efficacy of melittin were assessed in a xenograft mouse model.

Melittin inhibited the viability of CRC cell lines and induced apoptosis in SW480 cells by regulating apoptosis-related proteins. Melittin triggered endoplasmic reticulum (ER) stress and caused an imbalance in calcium homeostasis in SW480 cells. An absence of melittin triggered ER stress via the calcium chelating agent BAPTA/AM, and the IP3R inhibitor 2-aminoethoxydiphenyl borate (2-APB) impaired melittin-induced apoptosis in SW480 cells. Melittin treatment suppressed tumour growth but did not affect the body weight of SW480 tumour-bearing mice. Unlike cisplatin and 5-fluorouracil, melittin treatment did not change the biochemical and haematological parameters of the tumour-bearing mice. Finally, in these mice, melittin treatment induced ER stress, which was then blocked by BAPTA/AM, whilst 2-APB impaired the growth inhibitory effect of melittin.