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

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

doi:10.1371/journal.pone.0210274

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

PLoS One. 2019 Jan 18;14(1):e0210274. doi: 10.1371/journal.pone.0210274. eCollection 2019.

Authors

Tung-Cheng Chang^{1

2

3}, Po-Li Wei^{1

2

4

5

6}, Precious Takondwa Makondi^{1

7}, Wei-Ting Chen¹, Chien-Yu Huang^{2

3}, Yu-Jia Chang^{1

5

7}

Affiliations

¹ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁴ Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
⁵ Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
⁶ Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
⁷ International PhD Program in Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Autophagy*
Bromelains / pharmacology*
Cell Proliferation / drug effects*
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology*
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Reactive Oxygen Species / metabolism*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Zebrafish

Substances

Reactive Oxygen Species
Bromelains

Grants and funding

This work was supported by a grant form Taipei Medical University and Shuang Ho Hospital (105TMU-SHH-19). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.