Tanshinone IIA in colorectal cancer: preclinical mechanisms, therapeutic sensitization, and translational prospects
Abstract
Colorectal cancer (CRC) remains a major global health burden, with recurrence, metastasis, and therapeutic resistance limiting durable treatment responses. Tanshinone IIA (Tan IIA), a bioactive diterpene quinone derived from Salvia miltiorrhiza Bunge, has shown broad antitumor activity in preclinical CRC models. This review summarizes its major mechanisms, therapeutic-sensitization effects, and translational potential, while evaluating mechanistic evidence using a three-tier framework encompassing association, functional evidence, and mechanistically supported causality. Tan IIA inhibits proliferation, promotes apoptosis, disrupts mitochondrial and redox homeostasis, suppresses glycolytic adaptation, and modulates autophagy, ferroptosis, invasion, angiogenesis, and the inflammatory tumor microenvironment. It also enhances sensitivity to 5-fluorouracil and oxaliplatin in selected resistant models. Despite these preclinical findings, a substantial exposure gap exists between the nominal concentrations commonly used in CRC cell studies (5–40 μM) and the total plasma peak concentrations reported after oral Danshen administration in healthy volunteers (1.75–25.76 ng/mL). Clinical translation remains challenged by poor aqueous solubility, limited systemic exposure, metabolic clearance, and insufficiently defined exposure–response relationships and safety windows. Future studies should prioritize mechanistic validation and the assessment of pharmacologically active intratumoral exposure, alongside formulation optimization, structural modification, and systematic safety evaluation.
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BibTeX
@article{li2026tanshinone,
title = {{Tanshinone IIA in colorectal cancer: preclinical mechanisms, therapeutic sensitization, and translational prospects}},
author = {Siqin Li and Jingzhi Zhang and Xiaoyu Zhang and Zhihao Diao and Yiyang Sun and Yuxin Wu and Yi Zhang and Dongqing Du and Yuxia Ma},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1998852},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1998852},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tanshinone IIA in colorectal cancer: preclinical mechanisms, therapeutic sensitization, and translational prospects
AU - Siqin Li
AU - Jingzhi Zhang
AU - Xiaoyu Zhang
AU - Zhihao Diao
AU - Yiyang Sun
AU - Yuxin Wu
AU - Yi Zhang
AU - Dongqing Du
AU - Yuxia Ma
PY - 2026
DA - 2026/11/04
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1998852
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1998852
AB - Colorectal cancer (CRC) remains a major global health burden, with recurrence, metastasis, and therapeutic resistance limiting durable treatment responses. Tanshinone IIA (Tan IIA), a bioactive diterpene quinone derived from Salvia miltiorrhiza Bunge, has shown broad antitumor activity in preclinical CRC models. This review summarizes its major mechanisms, therapeutic-sensitization effects, and translational potential, while evaluating mechanistic evidence using a three-tier framework encompassing association, functional evidence, and mechanistically supported causality. Tan IIA inhibits proliferation, promotes apoptosis, disrupts mitochondrial and redox homeostasis, suppresses glycolytic adaptation, and modulates autophagy, ferroptosis, invasion, angiogenesis, and the inflammatory tumor microenvironment. It also enhances sensitivity to 5-fluorouracil and oxaliplatin in selected resistant models. Despite these preclinical findings, a substantial exposure gap exists between the nominal concentrations commonly used in CRC cell studies (5–40 μM) and the total plasma peak concentrations reported after oral Danshen administration in healthy volunteers (1.75–25.76 ng/mL). Clinical translation remains challenged by poor aqueous solubility, limited systemic exposure, metabolic clearance, and insufficiently defined exposure–response relationships and safety windows. Future studies should prioritize mechanistic validation and the assessment of pharmacologically active intratumoral exposure, alongside formulation optimization, structural modification, and systematic safety evaluation.
SN - 1663-9812
ER -