PSY Inhibits Colorectal Cancer Growth and Exhibits an In Vitro Synergistic Interaction with 5-Fluorouracil
4 affiliations
- 1Department of Biomedical Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea
- 2Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul 02454, Republic of Korea
- 3College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- 4BioNanocomposite Research Center, Kyung Hee University, Seoul 02447, Republic of Korea
Abstract
PSY is a three-herb formula comprising Patriniae Radix, Mori Cortex Radicis, and Coix Seed that was previously shown to inhibit STAT3 signaling in colorectal cancer (CRC) cells. Here, we investigated molecular and metabolic responses to PSY, its antitumor activity in an HCT116 xenograft model, and its interactions with chemotherapy in vitro. Representative chemical markers were qualitatively verified by UPLC-ESI-QTOF MS/MS. Exploratory RNA sequencing with two biological replicates per group highlighted stress-associated and metabolic processes for further investigation. PSY increased BiP, phosphorylated eIF2α, ATF4, and CHOP levels, intracellular reactive oxygen species (ROS) levels, and mitochondrial membrane depolarization, while reducing the phosphorylation of PI3K/AKT/mTOR- and ERK-associated proteins. PSY increased the p-AMPK/AMPK ratio and decreased the p-ACC/ACC ratio. PSY reduced several lipid-biosynthetic transcripts and decreased the relative abundance of selected fatty acids in xenograft tumors. Oral administration of PSY suppressed HCT116 xenograft growth without significant body-weight loss. Combination-index (CI) analysis indicated CI-defined in vitro synergistic interactions with 5-fluorouracil (5-FU) at multiple concentration pairs, with interaction patterns varying across HCT116, HT-29, and SW480 cells. Direct cell counting supported the combination response in HCT116 and SW480 cells. The combination increased apoptosis and reduced STAT3 and NF-κB p65 phosphorylation relative to single treatments. These findings characterize concurrent, partly discordant signaling and metabolic responses to PSY and support further preclinical evaluation of its in vitro interaction with 5-FU.
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BibTeX
@article{han2026inhibits,
title = {{PSY Inhibits Colorectal Cancer Growth and Exhibits an In Vitro Synergistic Interaction with 5-Fluorouracil}},
author = {Sanghee Han and Hail Kim and Hyunjin Choi and Minseo Oh and Min Young Lee and Junhee Lee and In Jin Ha and Kwang Seok Ahn and Seok-Geun Lee},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209238},
url = {https://www.mdpi.com/1422-0067/27/20/9238},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PSY Inhibits Colorectal Cancer Growth and Exhibits an In Vitro Synergistic Interaction with 5-Fluorouracil
AU - Sanghee Han
AU - Hail Kim
AU - Hyunjin Choi
AU - Minseo Oh
AU - Min Young Lee
AU - Junhee Lee
AU - In Jin Ha
AU - Kwang Seok Ahn
AU - Seok-Geun Lee
PY - 2026
DA - 2026/10/17
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209238
UR - https://www.mdpi.com/1422-0067/27/20/9238
AB - PSY is a three-herb formula comprising Patriniae Radix, Mori Cortex Radicis, and Coix Seed that was previously shown to inhibit STAT3 signaling in colorectal cancer (CRC) cells. Here, we investigated molecular and metabolic responses to PSY, its antitumor activity in an HCT116 xenograft model, and its interactions with chemotherapy in vitro. Representative chemical markers were qualitatively verified by UPLC-ESI-QTOF MS/MS. Exploratory RNA sequencing with two biological replicates per group highlighted stress-associated and metabolic processes for further investigation. PSY increased BiP, phosphorylated eIF2α, ATF4, and CHOP levels, intracellular reactive oxygen species (ROS) levels, and mitochondrial membrane depolarization, while reducing the phosphorylation of PI3K/AKT/mTOR- and ERK-associated proteins. PSY increased the p-AMPK/AMPK ratio and decreased the p-ACC/ACC ratio. PSY reduced several lipid-biosynthetic transcripts and decreased the relative abundance of selected fatty acids in xenograft tumors. Oral administration of PSY suppressed HCT116 xenograft growth without significant body-weight loss. Combination-index (CI) analysis indicated CI-defined in vitro synergistic interactions with 5-fluorouracil (5-FU) at multiple concentration pairs, with interaction patterns varying across HCT116, HT-29, and SW480 cells. Direct cell counting supported the combination response in HCT116 and SW480 cells. The combination increased apoptosis and reduced STAT3 and NF-κB p65 phosphorylation relative to single treatments. These findings characterize concurrent, partly discordant signaling and metabolic responses to PSY and support further preclinical evaluation of its in vitro interaction with 5-FU.
SN - 1422-0067
ER -