Jasmonates induce Arabidopsis bioactivities selectively inhibiting the growth of breast cancer cells through CDC6 and mTOR

Summary Phytochemicals are used often in vitro and in vivo in cancer research. The plant hormones jasmonates (JAs) control the synthesis of specialized metabolites through complex regulatory networks. JAs possess selective cytotoxicity in mixed populations of cancer and normal cells. Here, direct in...

Full description

Saved in:
Bibliographic Details
Published in:The New phytologist 2021-02, Vol.229 (4), p.2120-2134
Main Authors: Bömer, Moritz, Pérez‐Salamó, Imma, Florance, Hannah V., Salmon, Deborah, Dudenhoffer, Jan‐Hendrik, Finch, Paul, Cinar, Aycan, Smirnoff, Nicholas, Harvey, Amanda, Devoto, Alessandra
Format: Article
Language:English
Subjects:
Arabidopsis
Arabidopsis Proteins
Arabidopsis thaliana
bioassay
Biocompatibility
Biological activity
Breast cancer
Cancer
cancer therapy
Cell cycle
Cell Cycle Proteins
Cell division
Cell Line, Tumor
Cell viability
Cells
Crosstalk
Cyclin-dependent kinase 2
Cyclins
Cyclopentanes - pharmacology
Cytotoxicity
DNA
DNA biosynthesis
DNA replication
Explants
Herbal medicine
Hormones
Humans
Incubation
Incubation period
Indoles
jasmonate
Jasmonic acid
Kinases
Leaves
Medical treatment
Medicinal plants
Metabolites
natural compounds
Neoplasms
Organic compounds
Oxylipins - pharmacology
Plant Growth Regulators - pharmacology
Plant growth substances
Quinolines
Rapamycin
Regulators
Synergistic effect
TOR protein
TOR Serine-Threonine Kinases
Toxicity
Transcription
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Phytochemicals are used often in vitro and in vivo in cancer research. The plant hormones jasmonates (JAs) control the synthesis of specialized metabolites through complex regulatory networks. JAs possess selective cytotoxicity in mixed populations of cancer and normal cells. Here, direct incubation of leaf explants from the non‐medicinal plant Arabidopsis thaliana with human breast cancer cells, selectively suppresses cancer cell growth. High‐throughput LC‐MS identified Arabidopsis metabolites. Protein and transcript levels of cell cycle regulators were examined in breast cancer cells. A synergistic effect by methyljasmonate (MeJA) and by compounds upregulated in the metabolome of MeJA‐treated Arabidopsis leaves, on the breast cancer cell cycle, is associated with Cell Division Cycle 6 (CDC6), Cyclin‐dependent kinase 2 (CDK2), Cyclins D1 and D3, indicating that key cell cycle components mediate cell viability reduction. Bioactives such as indoles, quinolines and cis‐(+)‐12‐oxophytodienoic acid, in synergy, could act as anticancer compounds. Our work suggests a universal role for MeJA‐treatment of Arabidopsis in altering the DNA replication regulator CDC6, supporting conservation, across kingdoms, of cell cycle regulation, through the crosstalk between the mechanistic target of rapamycin, mTOR and JAs. This study has important implications for the identification of metabolites with anti‐cancer bioactivities in plants with no known medicinal pedigree and it will have applications in developing disease treatments
ISSN:0028-646X
1469-8137
DOI:10.1111/nph.17031