| Abstract |
Resveratrol has been shown to inhibit cell growth and induce apoptosis, as
well as augment chemotherapeutics and irradiation in multiple cancer types.
However, it is unknown if resveratrol is beneficial for treating drug-
resistant cancer cells. To study the effects of resveratrol in triple
negative breast cancer cells that are resistant to the common cancer drug,
paclitaxel, a novel paclitaxel-resistant cell line was generated from the
MDA-MB-231 breast cancer cell line. The resulting cell line, MDA-MB-231/PacR,
exhibited a 12-fold increased resistance to paclitaxel but
remained sensitive to resveratrol treatment. Resveratrol treatment reduced
cell proliferation and colony formation and increased senescence and
apoptosis in both the parental MDA-MB-231 and MDA-MB-231/PacR cell lines.
Importantly, resveratrol treatment augments the effects of paclitaxel in
both cell lines. The expression of the drug efflux transporter gene, MDR1,
and the main metabolizing enzyme of paclitaxel gene, CYP2C8, was increased
in the resistant cells. Moreover, pharmacological inhibition of the
protein products of these genes, P-glycoprotein and CYP2C8, decreased
paclitaxel resistance in the resistant but not in the parental cells,
which suggests that the increase of these proteins are important
contributors to the resistance of these cells. In conclusion, these
studies imply that resveratrol, both alone and in combination with
paclitaxel, may be useful in the treatment of paclitaxel-sensitive and
paclitaxel-resistant triple negative breast cancers.
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