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Research Article: PTPN1 downregulation contributes to pachymic acid-induced mitochondrial apoptosis in colorectal cancer cells

Date Published: 2026-10-13

Abstract:
Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Pachymic acid (PA), a bioactive triterpenoid derived from Poria cocos, exhibits antitumor activity, but its effects on CRC and the involvement of PTPN1 remain unclear. This study investigated whether PTPN1 downregulation contributes to PA-induced mitochondrial apoptosis in HCT-116 CRC cells. Cell proliferation and migration were evaluated using viability, DNA synthesis, colony formation, wound healing, and transwell assays. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis-related proteins, and the subcellular distribution of cytochrome c and Bax were examined. PTPN1 expression and overexpression rescue experiments were used to assess its functional involvement. PA inhibited cell proliferation and migration, increased ROS levels, and reduced mitochondrial membrane potential. These changes were accompanied by increased Bax, Bim, and cleaved caspase-3 expression, decreased Bcl-2 expression, and cytochrome c release from mitochondria into the cytoplasm. PA also downregulated PTPN1 expression. PTPN1 overexpression attenuated the effects of PA on proliferation, migration, ROS accumulation, mitochondrial membrane potential, and apoptosis-related protein expression. It also attenuated cytochrome c redistribution. These findings support a contribution of PTPN1 downregulation to PA-induced mitochondrial apoptosis in HCT-116 cells. Validation in additional CRC models, normal colonic epithelial cells, and in vivo systems is needed to establish the generalizability and therapeutic relevance of these findings.

Introduction:
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related death worldwide ( 1 , 2 ). Despite advancements in conventional therapies, the five-year survival rate for CRC remains below 20%, primarily due to its propensity for recurrence and metastasis ( 3 , 4 ). In 2020, the World Health Organization reported approximately 1.93 million new CRC cases globally ( 5 , 6 ). Despite ongoing progress in surgical techniques and targeted therapies, CRC prognosis…

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