Premium
Color‐coded chemotherapy: S/G2‐phase‐trapping by methioninase pre‐treatment, indicated by FUCCI imaging, enables highly effective cancer chemotherapy (923.11)
Author(s) -
Yano Shuya,
Tome Yasunori,
Digman Michelle,
Momiyama Masashi,
Suetsugu Atsushi,
Gratton Enrico,
Hoffman Robert
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.923.11
Subject(s) - chemotherapy , cancer cell , cisplatin , cancer , cell cycle , cancer research , methionine , cell , biology , chemistry , biochemistry , genetics , amino acid
Methionine deprivation by methionine α,γ lyase (methioninase or METase) selectively arrests cancer cells during late S/G2‐phase of the cell cycle, where the cancer cells are highly sensitive to DNA‐damaging chemotherapy. Fluorescent ubiquitination‐based cell cycle indicator (FUCCI) (Cell 132, 487‐498, 2008), was used to monitor the onset of the S/G2‐phase block due to methionine deprivation effected by METase. The S/G2‐phase‐blocked cancer cells fluoresced yellow or green, in contrast to cancer cells in G1/G0 which fluoresced red due to FUCCI. Cancer cells, synchronously blocked in S/G2‐phase by METase fluorescing yellow‐green, were treated with doxorubicin, cisplatin, or 5‐fluorouracil. As a control, cancer cells treated with drugs only without rMETAse, were resistant to the drugs. rMETase treatment, followed by chemotherapy, when FUCCI indicated the onset of S/G2 block, was highly effective. Color‐coded chemotherapy, whereby the cell cycle of cancer cells is blocked in S/G2‐phase, as identified by fluorescent reporters, may be a general approach to effective cancer treatment.