Paclitaxel: new uses for an old drug

Dongshan Zhang, Ruhao Yang, Shixuan Wang, Zheng Dong, Dongshan Zhang, Ruhao Yang, Shixuan Wang, Zheng Dong

Abstract

Paclitaxel (Taxol), one of the most important anticancer drugs, has been used for therapy of different types of cancers. Mechanistically, paclitaxel arrests cell cycle and induces cell death by stabilizing microtubules and interfering with microtubule disassembly in cell division. Recently, it has been found that low-dose paclitaxel seems promising in treating non-cancer diseases, such as skin disorders, renal and hepatic fibrosis, inflammation, axon regeneration, limb salvage, and coronary artery restenosis. Future studies need to understand the mechanisms underlying these effects in order to design therapies with specificity.

Keywords: coronary artery restenosis; fibrosis; kidney; limb salvage; taxol inflammation.

Figures

Figure 1
Figure 1
Chemical structure of paclitaxel.
Figure 2
Figure 2
Reported effects of paclitaxel in non-cancer diseases. Abbreviations: TLR-4, toll-like receptor 4; TGF-β, transforming growth factor-beta.
Figure 3
Figure 3
Anti-cancer actions of paclitaxel. Note: By stabilizing microtubules, paclitaxel arrests cell cycle in the G0/G1 and G2/M phases and induces cell death. Abbreviations: ROS, reactive oxygen species; MDSCs, myeloid-derived suppressor cells; AR, androgen receptor.
Figure 4
Figure 4
Paclitaxel inhibits TGF-β/Smad signaling via enhancing endogenous Smad2, Smad3 and Smad4 binding to microtubules, and thereby ameliorates fibrosis. Abbreviations: TGF-β, transforming growth factor-beta; Smad, mothers against decapentaplegic homolog; p, phosphorylated; R-I, TGFβ receptor I; R-II, TGFβ receptor II.
Figure 5
Figure 5
Paclitaxel inhibits inflammation by blocking TLR-4 signaling via binding to MD-2. Notes: Binding of paclitaxel (≥3.125 μM) to murine MD-2 results in the activation of MD-2/TLR-4 and promotes inflammation, whereas binding of paclitaxel to human MD-2, does not. Abbreviations: TLR-4, toll-like receptor 4; LPS, lipopolysaccharide; hMD-2, human MD-2; mMD-2, mouse MD-2.

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Source: PubMed

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