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Outline
Colorectal cancer (CRC) is a highly prevalent malignant tumor of the digestive system worldwide, and resistance to chemotherapy and immunotherapy constitutes a major challenge in its clinical management. While lipid metabolic reprogramming supports tumor proliferation, it also confers a specific metabolic susceptibility of CRC cells to ferroptosis, an iron-dependent form of programmed cell death driven by the accumulation of lipid peroxides. CRC cells promote the membrane incorporation of polyunsaturated fatty acids (PUFAs) by upregulating acyl-CoA synthetase long-chain family member 4 (ACSL4), reduce membrane lipid unsaturation by activating stearoyl-CoA desaturase 1 (SCD1), and rely on the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) antioxidant system, together with parallel pathways such as ferroptosis suppressor protein 1 (FSP1) and dihydroorotate dehydrogenase (DHODH), to eliminate peroxides and maintain the dynamic balance of the "lipid-ferroptosis axis". Owing to their multi-target regulatory advantages, natural bioactive compounds specifically intervene in this axis by inhibiting fatty acid desaturation, inducing lipophagic substrate mobilization, blocking antioxidant defenses, and disrupting iron homeostasis, thereby triggering ferroptosis in CRC cells. In addition, the combination of natural products with chemotherapeutic agents or immune checkpoint inhibitors can effectively reverse metabolism-adaptive resistance and activate antitumor immunity by inducing immunogenic ferroptosis. Given that clinical translation still faces challenges such as poor druggability and the lack of predictive models for therapeutic efficacy, the authors systematically analyzed the pharmacodynamic material basis and molecular mechanisms by which natural bioactive compounds modulate the lipid-ferroptosis axis, with the aim of providing a theoretical foundation for the development of drugs targeting metabolic remodeling and for the optimization of combination therapeutic strategies.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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