Cytotoxic properties of unfractionated and fractionated bromelain alone or in combination with chemotherapeutic agents in colorectal cancer cells.
PLoS One
; 18(6): e0285970, 2023.
Article
in En
| MEDLINE
| ID: mdl-37262048
ABSTRACT
BACKGROUND:
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain has been chromatographically separated into four fractions. Fraction 3 (F3) exhibits the highest proteolytic activity. The anticancer effects of F3 bromelain in CRC cells is unknown.METHODS:
In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit.RESULTS:
The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells.CONCLUSION:
Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC.
Full text:
1
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Colonic Neoplasms
/
Antineoplastic Agents
Language:
En
Journal:
PLoS One
Year:
2023
Type:
Article
Affiliation country:
Taiwan