# The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment
## 5 Perspectives and Limitations  
TSAIII, as a bioactive steroid saponin from _A. asphodeloides_, has potential anticancer effects in various cancer types. It regulates multiple cellular processes, including cellular proliferation, cell cycle, apoptosis, autophagy, migration, invasion, angiogenesis, multidrug \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Cancer Types** & **Cell Lines** & **Concentrations** & \begin{tabular}{c} **Key Molecular Targets or** \\ **Signaling Pathways** \\ \end{tabular} & **Effects** & **Refs.** \\ \hline \multirow{8}{*}{A549, H1299} & \multirow{8}{*}{A549, H1299} & \multirow{8}{*}{20 \(\mu\)M} & IC\({}_{50}\) = 1533 and 20.95 \(\mu\)M, & \multirow{8}{*}{\begin{tabular}{c} Induces autophagy \\ and apoptosis \\ \end{tabular} } \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \multirow{8}{*}{Lung cancer} & \multirow{8}{*}{A549/Taxol, 2/80/Taxol} & IC\({}_{50}\) = 5.12 and 4.64 \(\mu\)M, & \multirow{8}{*}{\begin{tabular}{c} Induces apoptosis \\ and inhibits \\ migration and \\ invasion \\ \end{tabular} } & \multirow{8}{*}{[74]} \\  & & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \multirow{8}{*}{Lung cancer} & \multirow{8}{*}{A549/Taxol, 2/80/Taxol} & IC\({}_{50}\) = 5.12 and 4.64 \(\mu\)M, & \multirow{8}{*}{\begin{tabular}{c} Induces apoptosis \\ and reverses drug \\ resistance \\ \end{tabular} } & \multirow{8}{*}{[90]} \\  & & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \multirow{8}{*}{Melanoma} & \multirow{8}{*}{A375-S2} & \multirow{8}{*}{2, 4, 6 \(\mu\)M} & Cell cycle G1 arrest, cleaved & \multirow{8}{*}{\
\begin{tabular}{c} Leaves cell cycle \\ and induces \\ autophagy and \\ apoptosis \end{tabular} } & \multirow{8}{*}{[62]} \\  & & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \multirow{8}{*}{Bone cancer} & \multirow{8}{*}{MG63} & \multirow{8}{*}{3, 6 \(\mu\)M} & \multirow{8}{*}{
\begin{tabular}{c}apoptotic rate\(\uparrow\), caspase-3\(\uparrow\), \\ migration\(\downarrow\), MMP-2\(\downarrow\), \\ MMP-9\(\downarrow\), p-ERK\(\downarrow\), p-JNK\(\downarrow\), \\ p-p-PSK\(\downarrow\), p-CREB\(\downarrow\), p-catenin\(\downarrow\) \\ \end{tabular} } & \multirow{8}{*}{[79]} \\  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & \\ \hline \multirow{8}{*}{Note: \(\uparrow\) indicates up-regulation, and \(\downarrow\) indicates down-regulation.} & \multirow{8}{*}{[71]} \\  & & & & & \\ \cline{1-1}  & & & & \\ \cline{1-1}  & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._resistance, inflammation, and oxidative stress, by upregulating or downregulating the expression of several key proteins that are involved in several signaling pathways. However, the signaling pathways mediated by TSAIII might be various due to the difference in cancer cell lines, models, and concentrations. It is challenging to investigate the alterations of a specific protein in different experimental models. It should be noted that TSAIII at a high concentration might potentially induce hepatotoxicity due to its activation of oxidative stress. Hopefully, other components in Zhimu, such as norathyriol and mangiferin, could act as antioxidants and exhibit hepatotoxicity activity indirectly. TSAIII can enhance the anticancer effects of several chemotherapy agents, such as ginseng Rg1, Rb1, and Rc. The synergistic effects of TSAIII are promising, and related clinical trials should be investigated. Due to the hydrophobicity and low bioavailability of TSAIII, effective delivery systems have been developed. Particularly, the tissue/cell-targeted delivery of TSAIII can significantly improve its anticancer effects. More efforts on the pharmacological activities of TSAIII are still needed. Several patents have been developed. For example, a preparation method for TSAIII has been developed by converting TSBII into TSAIII [106].