Hangeshashinto Induces Apoptosis and Suppresses Colorectal Cancer Growth In Vitro and In Vivo
5 affiliations
- 1Department of Personalized Kampo Medicine, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
- 2Department of Neurosurgery, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan
- 3Department of Nutrition Sciences, Graduate School of Health and Sports Sciences, Toyo University, Tokyo 115-8650, Japan
- 4Institution of Life Innovation Studies, Toyo University, Tokyo 115-8650, Japan
- 5Shizuoka Medical Research Center for Disaster, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan
Abstract
Hangeshashinto (HST) is a standardized seven-herb Kampo pharmaceutical used to manage gastrointestinal symptoms and chemotherapy-associated mucosal toxicity, but its direct antitumor activity remains insufficiently characterized. We examined the effects of HST in DLD-1 and SW480 colorectal cancer (CRC) cells and in non-malignant fibroblast and colonic epithelial cell models. Cell viability, colony formation, apoptosis-related endpoints, gene expression, responses to 5-fluorouracil (5-FU), and the activity of representative constituents were evaluated. Oral antitumor efficacy and tolerability were assessed in female BALB/c-nu mice bearing DLD-1 xenografts. HST preferentially reduced CRC cell viability and colony formation and increased annexin V positivity, caspase-3 activity, cleaved caspase-3 staining, and apoptotic nuclear changes. z-VAD-FMK showed a nonsignificant tendency toward partial recovery of cell viability. Reverse transcription–quantitative polymerase chain reaction findings were exploratory; statistical significance was not assessed. Co-treatment with HST (0.3 mg/mL) and 5-FU significantly reduced cell viability compared with 5-FU alone in both DLD-1 and SW480 cells; pharmacological synergy was not evaluated. Oral HST inhibited xenograft growth; tolerability assessment was limited to body weight and serum biochemistry, with reduced serum uric acid in the high-dose group after washout. These findings provide a preclinical basis for further investigation of standardized HST in CRC.
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BibTeX
@article{lin2026hangeshashinto,
title = {{Hangeshashinto Induces Apoptosis and Suppresses Colorectal Cancer Growth In Vitro and In Vivo}},
author = {Yunhai Lin and Jingya Lu and Ailing Hu and Takuji Yamaguchi and Yasushi Ikarashi and Yoshinao Harada and Kaho Ohki and Takumi Iwasawa and Hiroyuki Kobayashi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209310},
url = {https://www.mdpi.com/1422-0067/27/20/9310},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hangeshashinto Induces Apoptosis and Suppresses Colorectal Cancer Growth In Vitro and In Vivo
AU - Yunhai Lin
AU - Jingya Lu
AU - Ailing Hu
AU - Takuji Yamaguchi
AU - Yasushi Ikarashi
AU - Yoshinao Harada
AU - Kaho Ohki
AU - Takumi Iwasawa
AU - Hiroyuki Kobayashi
PY - 2026
DA - 2026/10/20
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209310
UR - https://www.mdpi.com/1422-0067/27/20/9310
AB - Hangeshashinto (HST) is a standardized seven-herb Kampo pharmaceutical used to manage gastrointestinal symptoms and chemotherapy-associated mucosal toxicity, but its direct antitumor activity remains insufficiently characterized. We examined the effects of HST in DLD-1 and SW480 colorectal cancer (CRC) cells and in non-malignant fibroblast and colonic epithelial cell models. Cell viability, colony formation, apoptosis-related endpoints, gene expression, responses to 5-fluorouracil (5-FU), and the activity of representative constituents were evaluated. Oral antitumor efficacy and tolerability were assessed in female BALB/c-nu mice bearing DLD-1 xenografts. HST preferentially reduced CRC cell viability and colony formation and increased annexin V positivity, caspase-3 activity, cleaved caspase-3 staining, and apoptotic nuclear changes. z-VAD-FMK showed a nonsignificant tendency toward partial recovery of cell viability. Reverse transcription–quantitative polymerase chain reaction findings were exploratory; statistical significance was not assessed. Co-treatment with HST (0.3 mg/mL) and 5-FU significantly reduced cell viability compared with 5-FU alone in both DLD-1 and SW480 cells; pharmacological synergy was not evaluated. Oral HST inhibited xenograft growth; tolerability assessment was limited to body weight and serum biochemistry, with reduced serum uric acid in the high-dose group after washout. These findings provide a preclinical basis for further investigation of standardized HST in CRC.
SN - 1422-0067
ER -