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Journal of Cancer Prevention

Original Article

J Cancer Prev 2022; 27(2): 112-121

Published online June 30, 2022

© Korean Society of Cancer Prevention

Formoxanthone C Inhibits Malignant Tumor Phenotypes of Human A549 Multidrug Resistant-cancer Cells through Signal Transducer and Activator of Transcription 1-Histone Deacetylase 4 Signaling

Chutima Kaewpiboon1,* , Nawong Boonnak2 , Sirichat Kaowinn3 , Natpaphan Yawut4 , Young-Hwa Chung4,*

1Department of Biology, Faculty of Science, Thaksin University, Phatthalung, 2Department of Basic Science and Mathematics, Faculty of Science, Thaksin University, Songkhla, 3Department of General Science and Liberal Arts, King Mongkut’s Institute of Technology Ladkrabang Prince of Chumphon Campus, Chumphon, Thailand, 4Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Korea

Correspondence to :
Chutima Kaewpiboon, E-mail:,
Young-Hwa Chung, E-mail:,
*These authors contributed equally to this work as co-correspondence authors.

Received: April 21, 2022; Revised: June 9, 2022; Accepted: June 9, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Considering that presence of cancer stem cell (CSC) subpopulation in tumor tissues confers anticancer drug resistance, we investigated whether human A549 lung cancer cells resistant to etoposide possess CSC-like phenotypes. Furthermore, it is known that these malignant tumor features are the leading cause of treatment failure in cancer. We have thus attempted to explore new therapeutic agents from natural products targeting these malignancies. We found that formoxanthone C (XanX), a 1,3,5,6-tetraoxygenated xanthone from Cratoxylum formosum ssp. pruniflorum, at a non-cytotoxic concentration reduced the expression of the signal transducer and activator of transcription 1 (STAT1) and histone deacetylase 4 (HDAC4) proteins, leading to inhibition of CSC-like phenotypes such as cell migration, invasion, and sphere-forming ability. Moreover, we found that treatment with STAT1 or HDAC4 small interfering RNAs significantly hindered these CSC-like phenotypes, indicating that STAT1 and HDAC4 play a role in the malignant tumor features. Taken together, our findings suggest that XanX may be a potential new therapeutic agent targeting malignant lung tumors.

Keywords: Formoxanthone C, Multidrug resistant-cancer, Cancer stem cell-like phenotypes, Signal transducer and activator of transcription 1, Histone deacetylase 4

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