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Journal of Materials Science and Nanotechnology | Volume: 2
November 22-23, 2018 | Paris, France
Materials Physics and Materials Science
International Conference on
Increasing evidence points to a connection between protein
synthesis and cancer cells growth. For example, cycloheximide
that had been shown to be a strong inhibitor of eucaryotic
translation, was also shown to inhibit cancer cells growth in vitro
and in vivo, suggesting that this translation inhibitor may serve
as lead in the development of new cancer therapeutics. Here,
by combining affinity labeling studies and mass spectrometric
analyses on human 80S or E. coli 70S ribosomes, we have
identified the ribosomal proteins (rPs) targeted by the small-
molecule inhibitors of translation. These are rP-eL42 of human
80S ribosomes and rPbL12 of E. coli 70S ribosomes. We have
recently demonstrated that these rPs assist catalysis of peptide
bond formationat theelongation stepof translation. Thehuman
rP-eL42 was previously shown to be overexpressed in human
hepatocellularcarcinoma(HCC)aswellasinseveralhumantumor
cell-lines, while an increased exposure of intestine to bacterial
rPbL12 was previously observed in colorectal cancer patients.
It is generally accepted that ribosomal protein overexpression
might promote tumorigenesis by interactions with the p53
tumor suppressor pathway, and that these overexpressed
proteins could represent targets for cancer therapy. Therefore,
we have designed anticancer drugs analogous to cycloheximide
capable of targeting rPs eL42 and bL12 in order to block the
hyper-proliferation of tumor cells by reducing the rate of
protein synthesis. These molecules are thiosemicarbazones,
two of which having a potent antiproliferative effect on tumor
cell lines and selectively inhibiting translation. They are now
ready to undergo clinical trials.
Speaker Biography
Codjo Hountondji is distinguished professor at Sorbonne University (Campus Pierre et
Marie Curie, Jussieu, Paris) where he has been teaching biochemistry and molecular
Biology for 35 years. He is currently director of the research Group “Enzymology of
RNA”. He has served as assistant professor of Biochemistry at the University Paris XI
(Orsay) 1982-1986. At the University Pierre et Marie Curie (Paris), he has served as chair
of the division (department of biochemistry and molecular biology 2010-2014). He has
been a visiting scientist at Penn State University School of Medicine in Philadelphia in
1981-1982. He published more than 40 research papers and articles in international
journals. He supervised numerous master and PhD students for their research projects.
His career research focus has been on the mechanism of the translation process. His
current research interest concerns a “Targeted molecular therapy of cancer: Structure-
assisted design of anticancer drugs targeting the ribosomes in cancer cells”.
e:
Codjo Hountondji
Sorbonne University, France
Mass Spectrometric identification of a ribosomal protein promotor of cancer, targeted
by anticancer drugs