Journal Article

Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy

Huang, Chien-Yu, Chen, Wei-Ting, Chang, Tung-Cheng, Wei, Po-Li, Makondi, Precious Takondwa, Chang, Yu-Jia

2019

Overview

Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenosine diphosphate / Animal models / Animals / Anticancer properties / Apoptosis / Apoptosis - drug effects / Autophagy / Autophagy (Cytology) / Biology and Life Sciences / Biotechnology / Bromelain / Bromelains - pharmacology / Cancer / Cancer therapies / Care and treatment / Caspase / Caspase-3 / Caspase-8 / Caspase-9 / Cell death / Cell growth / Cell Proliferation - drug effects / Clinical medicine / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - metabolism / Colorectal Neoplasms - pathology / Cytokines / Cytotoxicity / Danio rerio / Development and progression / Embryos / Gene expression / Genetic aspects / Hospitals / Humans / Kinases / Laboratories / Lysosomes / Male / Medical research / Medicine / Medicine and Health Sciences / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Microscopy / Oxidative stress / Oxygen / Patient outcomes / Phagocytosis / Phagosomes / Physical Sciences / Poly(ADP-ribose) polymerase / Proteins / Reactive oxygen species / Reactive Oxygen Species - metabolism / Research and Analysis Methods / Ribose / Superoxide / Surgery / Survival / Tumor cell lines / Tumor Cells, Cultured / Xenograft Model Antitumor Assays / Xenografts / Xenotransplantation / Zebrafish