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Review
. 2024 Nov 15;15(1):658.
doi: 10.1007/s12672-024-01510-2.

The potential of kaempferol in digestive system tumors: recent advances and mechanistic insights

Xunxing Hao #  1 , Meng Ding #  1 , Chenyu Chi  2 , Xiaodong Xu  3 , Xiaoyu Zhang  4 , Mingzhe Hu  5
Affiliations
Review

The potential of kaempferol in digestive system tumors: recent advances and mechanistic insights

Xunxing Hao et al. Discov Oncol. .

Abstract

Digestive system neoplasms are a heterogeneous group of cancers characterized by diverse symptoms, complex diagnosis, and treatment. Prognosis is poor and influenced by multiple factors, making early detection and comprehensive treatment crucial for patient survival. Kaempferol, a flavonoid compound, has attracted attention due to its anti-tumor biological activity, holding promise as a potential drug for treating digestive system neoplasms. Derived from various plants such as cabbage, propolis, and grapefruit, this compound's anti-inflammatory, antioxidant, and other pharmacological effects have been confirmed. Research has found that kaempferol inhibits the occurrence and development of digestive system neoplasms by inducing apoptosis in cancer cells, inhibiting tumor cell proliferation, suppressing tumor metastasis and invasion, and enhancing the effects of other cancer treatment methods. This paper summarizes the role and mechanisms of kaempferol in the study of digestive system neoplasms, providing valuable insights for both scientists and clinical physicians engaged in this field. By detailing the various pathways through which kaempferol exerts its anticancer effects, the paper not only highlights its potential as a therapeutic agent but also opens avenues for further research into its applications.

Keywords: Digestive system neoplasms; Flavonoids; Kaempferol; Mechanism; Pathway.

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Conflict of interest statement

Declarations Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Kaempferol is a flavonoid compound widely found in natural plants and traditional herbs such as Ginkgo leaves, tomatoes, and propolis. It exerts anti-tumor effects on the digestive system through several mechanisms, including inducing apoptosis, inhibiting the proliferation and invasion of digestive system tumor cells, and regulating autophagy in tumor cells
Fig. 2
Fig. 2
The figure illustrates how kaempferol induces apoptosis in digestive system tumors. Kaempferol promotes apoptosis through the regulation of Caspases, Bik, PARP, and Bcl-xL, while also inhibiting cancer cell proliferation by reducing Ki67 and LGR5 expression. Additionally, kaempferol enhances miR-326, which targets PKM2, thereby suppressing glycolysis and overcoming drug resistance. It reduces oxidative stress markers and regulates apoptosis-related genes through various mechanisms, including ROS-dependent apoptosis via the Akt/mTOR pathway and inflammasome activation through NF-κB signaling
Fig. 3
Fig. 3
The figure illustrates how kaempferol inhibits digestive system tumors cell proliferation. Kaempferol modulates the miR-339-5p-hnRNPA1/PTBP1-PKM1/2 axis to suppress glycolysis. It also regulates p21 expression via miR-92a/31, inhibits oncogenic pathways involving KRAS and MAPK, and reduces c-MYC and HIF-1 expression. Additionally, it blocks the G2/M phase of the cell cycle and promotes apoptosis by modulating Bcl-2, Bax, and caspase-3 activity
Fig. 4
Fig. 4
The figure shows how kaempferol suppresses metastasis and invasion while inducing autophagy in digestive system tumors. Kaempferol suppresses migration by targeting EGFR-related Src, ERK1/2, and AKT pathways, and promotes autophagic cell death via the IRE1-JNK-CHOP pathway. It induces G2/M cell cycle arrest and autophagic death through CDK1/cyclin B regulation and AMPK/AKT signaling. Additionally, it enhances autophagy by increasing the conversion of LC3-I to LC3-II
Fig. 5
Fig. 5
The figure illustrates the mechanism by which kaempferol enhances sensitivity to anti-digestive system tumor drugs. Kaempferol plays a crucial role in overcoming 5-Fluorouracil resistance by regulating the miR-326-hnRNPA1/A2/PTBP1-PKM2 axis. It inhibits 5-Fluorouracil resistance through the modulation of JAK/STAT3, MAPK, PI3K/AKT, and NF-κB expression. When combined with TRAIL, kaempferol upregulates the expression of TRAIL receptors DR5 and DR4, leading to induced apoptosis in tumor cells. Additionally, kaempferol enhances the sensitivity of pancreatic cancer cells to Erlotinib by inhibiting the EGFR and PI3K/AKT signaling pathways. Furthermore, in combination with Doxorubicin, kaempferol suppresses the migration and invasion of liver cancer cells by inhibiting the PI3K/mTOR/MMP signaling pathway
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