Jasmonates induce Arabidopsis bioactivities selectively inhibiting the growth of breast cancer cells through CDC6 and mTOR. / Bomer, Moritz; Perez-Salamo, Imma; Florance, Hannah; Salmon, Debbie; Dudenhoffer, Jan-Hendrik ; Finch, Paul; Cinar, Aycan; Smirnoff, Nicholas; Harvey, Amanda ; Devoto, Alessandra.

In: New Phytologist, Vol. 229, No. 4, 29.10.2020, p. 2120-2134.

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Abstract

Phytochemicals are often used 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. Proteins 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 CDC6, CDK2, CYCD1 and CYCD3, indicating that key cell cycle components mediates cell viability reduction. Bioactives such as indoles and quinolines and OPDA, 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 target of rapamycin, mTOR, and JAs.
This study has important implications to identify metabolites with anti-cancer bioactivities in plants with no known medicinal pedigree and it will have applications in developing disease treatments.
Original languageEnglish
Pages (from-to)2120-2134
Number of pages15
JournalNew Phytologist
Volume229
Issue number4
Early online date29 Oct 2020
DOIs
Publication statusE-pub ahead of print - 29 Oct 2020
This open access research output is licenced under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

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