Taccalonolide

[1] While taxanes like paclitaxel and docetaxel have been used successfully against breast, ovarian, prostate, and non–small-cell lung cancers, intrinsic and acquired drug resistance limit their anticancer properties.

The potential advantages of taccalonolides include: 1) a novel structure, 2) a novel mechanism, 3) more persistent (less reversible) activity than other MT-stabilizers, and 4) concentrations effective in interphase and mitotic cells that are very similar.

[1][10] However, taccalonolides A,B,E, and N have shown cytotoxic potency in the high nanomolar range against cervical, ovarian, breast, and lung cancer cell lines.

[1][10] Because they do not bind directly to tubulin, taccalonolides have shown efficacy in cell lines and tumors with taxane-resistance mediated by overexpression of P-glycoprotein (Pgp) multidrug transporter or expression of class III β-tubulin.

[10] Taccalonolides A and E were potent against Pgp-expression Mam17/ADR synergeic cells in mouse models and were shown to be effective antitumor agents in doxorubicin and paclitaxel insensitive tumors.

[7] Finally, it is imperative to elucidate the mechanism of action of taccalonides to further both drug development and identification of other molecules capable of producing taccalonolide-like effects.