Colon cancer (CC) is one of the major causes of cancer death in humans. Despite recent advances in the management of CC, the prognosis is still poor and a new strategy for effective therapy is imperative. Deoxyelephantopin (DET), extracted from an important medicinal plant, Elephantopus scaber L., has been reported to exhibit excellent anti-inflammatory and -cancer activities, while the detailed anti-cancer mechanism remains unclear. Herein, we found that DET showed a significant CC inhibiting effect in vitro and in vivo without obvious organ toxicity. Mechanistically, DET inhibited CC cells and tumor growth by inducing G2/M phase arrest and subsequent apoptosis. DET-mediated cell cycle arrest was caused by severe DNA damage, and DET decreased the Bcl2 expression level in a dose-dependent manner to promote CC cell apoptosis, whereas restoring Bcl2 expression reduced apoptosis to a certain extent. Moreover, we identified a microRNA complementary to the 3′-UTR of Bcl2, miR-205, that responded to the DET treatment. An inhibitor of miR-205 could recover Bcl2 expression and promoted the survival of CC cells upon DET treatment. To further examine the potential value of the drug, we evaluated the combinative effects of DET and 5-Fluorouracil (5FU) through Jin’s formula and revealed that DET acted synergistically with 5FU, resulting in enhancing the chemotherapeutic sensitivity of CC to 5FU. Our results consolidate DET as a potent drug for the treatment of CC when it is used alone or combined with 5FU, and elucidate the importance of the miR-205-Bcl2 axis in DET treatment.

Chemodynamic therapy (CDT) has garnered significant interest as an innovative approach for cancer treatment, owing to its notable tumor specificity and selectivity, minimal systemic toxicity and side effects, and absence of the requirement for field stimulation during treatment. This treatment utilizes nanocatalytic medicines containing transitional metals to release metal ions within tumor cells, subsequently initiating Fenton and Fenton-like reactions. These reactions convert hydrogen peroxide (H₂O₂) into hydroxyl radical (•OH) specifically within the acidic tumor microenvironment (TME), thereby inducing apoptosis in tumor cells. However, insufficient endogenous H₂O₂, the overexpressed reducing substances in the TME, and the weak acidity of solid tumors limit the performance of CDT and restrict its application in vivo. Therefore, a variety of nanozymes and strategies have been designed and developed in order to potentiate CDT against tumors, including the application of various nanozymes and different strategies to remodel TME for enhanced CDT (e.g., increasing the H₂O₂ level in situ, depleting reductive substances, and lowering the pH value). This review presents an overview of the design and development of various nanocatalysts and the corresponding strategies employed to enhance catalytic drug targeting in recent years. Additionally, it delves into the prospects and obstacles that lie ahead for the future advancement of CDT.