CPF impedes cell cycle re-entry of quiescent lung cancer cells through transcriptional suppression of FACT and c-MYC

Ling Bi; Chanlu Xie; Lijing Jiao; Shenyi Jin; Su Su Thae Hnit; Yao Mu; Yilun Wang; Qian Wang; Guangbo Ge; Yaqiao Wang; Xiaodong Zhao; Xinglong Shi; Yani Kang; Paul De Souza; Tao Liu; Jia Zhou; Ling Xu; Qihan Dong

doi:10.1111/jcmm.14897

CPF impedes cell cycle re-entry of quiescent lung cancer cells through transcriptional suppression of FACT and c-MYC

J Cell Mol Med. 2020 Feb;24(3):2229-2239. doi: 10.1111/jcmm.14897. Epub 2020 Jan 20.

Authors

Ling Bi¹, Chanlu Xie^{2

3

4}, Lijing Jiao¹, Shenyi Jin¹, Su Su Thae Hnit^{2

3

4}, Yao Mu^{3

4}, Yilun Wang^{3

4}, Qian Wang^{5

6}, Guangbo Ge⁷, Yaqiao Wang⁷, Xiaodong Zhao⁸, Xinglong Shi⁸, Yani Kang⁹, Paul De Souza¹⁰, Tao Liu^{11

12}, Jia Zhou¹³, Ling Xu¹, Qihan Dong^{2

3

4}

Affiliations

¹ Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² School of Science and Health, National Institute of Complementary Medicine, Western Sydney University, Penrith South, NSW, Australia.
³ Chinese Medicine Anti-cancer Evaluation Program, Greg Brown Laboratory, Central Clinical School and Charles Perkins Center, The University of Sydney, Sydney, NSW, Australia.
⁴ Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
⁵ Origins of Cancer Program, Centenary Institute, Camperdown, NSW, Australia.
⁶ Sydney Medical School, the University of Sydney, Sydney, NSW, Australia.
⁷ Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁸ Shanghai Center for Systems Biology, Shanghai Jiao Tong University, Shanghai, China.
⁹ School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
¹⁰ School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
¹¹ Children's Cancer Institute Australia for Medical Research, Sydney, NSW, Australia.
¹² Center for Childhood Cancer Research, UNSW Medicine, Sydney, NSW, Australia.
¹³ Department of Thoracic Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Blockade of cell cycle re-entry in quiescent cancer cells is a strategy to prevent cancer progression and recurrence. We investigated the action and mode of action of CPF mixture (Coptis chinensis, Pinellia ternata and Fructus trichosanthis) in impeding a proliferative switch in quiescent lung cancer cells. The results indicated that CPF impeded cell cycle re-entry in quiescent lung cancer cells by reduction of FACT and c-MYC mRNA and protein levels, with concomitant decrease in H3K4 tri-methylation and RNA polymerase II occupancy at FACT and c-MYC promoter regions. Animals implanted with quiescent cancer cells that had been exposed to CPF had reduced tumour volume/weight. Thus, CPF suppresses proliferative switching through transcriptional suppression of FACT and the c-MYC, providing a new insight into therapeutic target and intervention method in impeding cancer recurrence.

Keywords: G0 cell cycle re-entry; c-MYC; lung cancer; structure-specific recognition protein 1; suppressor of Ty homolog-16.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Animals
Araceae / chemistry
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
DNA-Binding Proteins / genetics*
High Mobility Group Proteins / genetics*
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Plant Extracts / pharmacology*
Promoter Regions, Genetic / drug effects
Proto-Oncogene Proteins c-myc / genetics*
RNA, Messenger / genetics
Ranunculaceae / chemistry
Transcription, Genetic / drug effects*
Transcriptional Elongation Factors / genetics*
Trichosanthes / chemistry

Substances

DNA-Binding Proteins
High Mobility Group Proteins
MYC protein, human
Plant Extracts
Proto-Oncogene Proteins c-myc
RNA, Messenger
SSRP1 protein, human
Transcriptional Elongation Factors