Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A

SummaryChemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7. Doxorubicin, a DNA-damaging agent, paclitaxel, and discodermolide were used as positive controls. Senescence-associated- β-galactosidase activity was increased by peloruside A, similar to paclitaxel, discodermolde, and doxorubicin, with a potency hei...

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