Targeting oncogenic mutations in colorectal cancer using cryptotanshinone.
Colorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem...
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Online Access: | https://doi.org/10.1371/journal.pone.0247190 |
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doaj-4ba83b411b674c0b96a6f62f387a81612021-08-15T04:30:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e024719010.1371/journal.pone.0247190Targeting oncogenic mutations in colorectal cancer using cryptotanshinone.Haswanth VundavilliAniruddha DattaChao SimaJianping HuaRosana LopesMichael BittnerColorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem from multiple oncogenic mutations and crosstalk between abnormal pathways. This calls for using advanced molecular genetics to understand the underlying pathway interactions responsible for this cancer. In this paper, we construct the CRC pathway from the literature and using an existing public dataset on healthy vs tumor colon cells, we identify the genes and pathways that are mutated and are possibly responsible for the disease progression. We then introduce drugs in the CRC pathway, and using a boolean modeling technique, we deduce the drug combinations that produce maximum cell death. Our theoretical simulations demonstrate the effectiveness of Cryptotanshinone, a traditional Chinese herb derivative, achieved by targeting critical oncogenic mutations and enhancing cell death. Finally, we validate our theoretical results using wet lab experiments on HT29 and HCT116 human colorectal carcinoma cell lines.https://doi.org/10.1371/journal.pone.0247190 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haswanth Vundavilli Aniruddha Datta Chao Sima Jianping Hua Rosana Lopes Michael Bittner |
spellingShingle |
Haswanth Vundavilli Aniruddha Datta Chao Sima Jianping Hua Rosana Lopes Michael Bittner Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. PLoS ONE |
author_facet |
Haswanth Vundavilli Aniruddha Datta Chao Sima Jianping Hua Rosana Lopes Michael Bittner |
author_sort |
Haswanth Vundavilli |
title |
Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. |
title_short |
Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. |
title_full |
Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. |
title_fullStr |
Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. |
title_full_unstemmed |
Targeting oncogenic mutations in colorectal cancer using cryptotanshinone. |
title_sort |
targeting oncogenic mutations in colorectal cancer using cryptotanshinone. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2021-01-01 |
description |
Colorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem from multiple oncogenic mutations and crosstalk between abnormal pathways. This calls for using advanced molecular genetics to understand the underlying pathway interactions responsible for this cancer. In this paper, we construct the CRC pathway from the literature and using an existing public dataset on healthy vs tumor colon cells, we identify the genes and pathways that are mutated and are possibly responsible for the disease progression. We then introduce drugs in the CRC pathway, and using a boolean modeling technique, we deduce the drug combinations that produce maximum cell death. Our theoretical simulations demonstrate the effectiveness of Cryptotanshinone, a traditional Chinese herb derivative, achieved by targeting critical oncogenic mutations and enhancing cell death. Finally, we validate our theoretical results using wet lab experiments on HT29 and HCT116 human colorectal carcinoma cell lines. |
url |
https://doi.org/10.1371/journal.pone.0247190 |
work_keys_str_mv |
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