melitten and Colorectal-Neoplasms

The primary goal of the current study was to investigate the effect of melittin on colorectal cancer (CRC).. 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.. Melittin treatment inhibits CRC progression by inducing ER stress and an imbalance in calcium homeostasis.

Topics: Animals; Apoptosis; Calcium; Cell Line, Tumor; Colorectal Neoplasms; Endoplasmic Reticulum Stress; Humans; Melitten; Mice

Cancer is a multifaceted health issue that affects people globally and it is considered one of the leading causes of death with a high percentage of victims worldwide. In recent years, research studies have uncovered great advances in cancer diagnosis and treatment. But, there are still major drawbacks of the conventional therapies used including severe side effects, toxicity, and drug resistance. That is why it is critical to develop new drugs with advantages like low cytotoxicity and no treatment resistance to the cancer cells. Antimicrobial peptides (AMPs) have recently attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tumor cells with less toxicity to normal tissues. The aim of the study was to discover alternate treatments that do not lead to cancer resistance and have fewer side effects. Here, we report the effects induced by several AMPs, Melittin, Cecropin A, and a Cecropin A-Melittin hybrid, against two human colorectal cancer-derived spheroids. To study the effects of the peptides, cell viability was investigated using MTT, LDH, and ATP assays. Furthermore, cellular senescence and cell cycle were investigated. We found that using different concentrations of these peptides affected the spheroids, their structure being highly compromised by reducing cell viability, and the increase in ATP and LDH levels. Also, the cells are arrested in the G2/M phase leading to an increase in senescent cells. We show that Melittin and the hybrid are most effective against the 3D colorectal cancer cells compared to Cecropin A.

Topics: Adenosine Triphosphate; Anti-Bacterial Agents; Antimicrobial Peptides; Colorectal Neoplasms; Humans; Melitten

The cytotoxic effects of melittin, a bee-venom peptide, have been widely studied towards cancer cells. Typically, these studies have examined the effect of melittin over extended-time courses (6-24 hours), meaning that immediate cellular interactions have been overlooked. In this work, we demonstrate the rapid effects of melittin on both gastric and colorectal cancer, specifically AGS, COLO205 and HCT-15 cell lines, over a period of 15 minutes. Melittin exhibited a dose dependent effect at 4 hours of treatment, with complete cellular death occurring at the highest dose of 20 μg/mL. Interestingly, when observed at shorter time points, melittin induced cellular changes within seconds; membrane damage was observed as swelling, breakage or blebbing. High-resolution imaging revealed treated cells to be compromised, showing clear change in cellular morphology. After 1 minute of melittin treatment, membrane changes were observed, and intracellular material could be seen expelled from the cells. Overall, these results enhance our understanding of the fast acting anti-cancer effects of melittin.

Topics: Antineoplastic Agents; Apoptosis; Bee Venoms; Cell Line, Tumor; Cell Membrane; Colorectal Neoplasms; Humans; Melitten; Microscopy, Atomic Force; Microscopy, Fluorescence; Stomach Neoplasms