A comprehensive overview on the anti-inflammatory, antitumor, and ferroptosis functions of bromelain: an emerging cysteine protease

ABSTRACT

Introduction

Bromelain belongs to the cysteine protease endopeptidase class of enzymes isolated from the stem and fruit tissue component of Ananas comosus. The commercial and translational therapeutic potential of bromelain is ever increasing due to its augmented stability, easier purification, and salubrious pan-cancer effects.

Areas Covered

This paper presents the current state of knowledge about the isolation methods of bromelain, its safety, efficacy and tolerability. In addition, bromelains’ role in eliciting pharmacological effects and its healing ability to mitigate cancer side effects based on accumulated in vitro, in vivo, and clinical evidence is relatively considerable.

Expert Opinion

Identification of molecular targets and crucial signalling pathways that bromelain regulates suggest it genuinely prospects for combating cancer and mitigation of chemotherapy or radiotherapy mediated side effects. Further research on the development of bromelain-entrapped drug delivery systems for augmented enzyme stability, processing ability and translational potential against cancer can be beneficial.

KEYWORDS:

• Cysteine protease
• stem bromelain
• nuclear factor-kappa B
• anticancer
• pineapple

Article highlights

• Acetone precipitation method provides better yield and enhanced stability of bromelain; however, the reverse micellar evaporation method provides higher protease specificity.

• Bromelain in vitro and in vivo possesses promising pan-cancer effects due to its ability to regulate various molecular targets and signalling pathways linked to inflammation, tumour growth and ferroptosis.

• Bromelain at a molecular level prevents inflammation, causes cell cycle arrest, suppresses proliferation, mitigates tumour niche, abrogates metastasis, modulates the immune response, and facilitates ferroptosis.

• Bromelain alleviates the side effects mediated by chemotherapy and radiotherapy cancer treatment approaches.

• Bromelain as a clinical modality in humans suggests promising results in alleviating side effects of the mucinous peritoneal tumour and breast cancer.

• Prospects of developing nano-delivery systems with enhanced protease activity or sustained release of bromelain is warranted against cancer.

This box summarizes key points contained in the article.

Acknowledgments

We place on record our most profound sense of gratitude to SRM IST for providing constant motivation and support to submit this work.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.