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柑橘类黄酮橙皮素对PPC-1人前列腺癌细胞中紫杉烷细胞毒性的抑制作用。

Suppression of Taxanes Cytotoxicity by Citrus Flavonoid Hesperetin in PPC-1 Human Prostate Cancer Cells.

作者信息

Sak Katrin, Lust Helen, Kase Marju, Saar Marika, Jaal Jana

机构信息

Clinic of Hematology and Oncology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia

Clinic of Hematology and Oncology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.

出版信息

Anticancer Res. 2018 Nov;38(11):6209-6215. doi: 10.21873/anticanres.12975.

Abstract

BACKGROUND/AIM: More than half of prostate cancer patients use, in addition to conventional therapies, some kind of complementary medicine, including flavonoid-rich products. However, knowledge about the co-effects of flavonoids with cytotoxic chemotherapies is still rather poor. Therefore, this study was undertaken to assess the cytotoxic activity of flavonoids and their interactions with taxanes in human advanced prostate cancer cells.

MATERIALS AND METHODS

Cytotoxicity of different flavonoids and their effects on the efficacy of docetaxel and cabazitaxel were studied in the human metastatic prostate cancer cell line PPC-1, using MTT colorimetric assay.

RESULTS

Both taxanes suppressed the viability of PPC-1 cells with IC values in the nanomolar range. Tested flavonoids exerted cytotoxic activity only at high micromolar concentrations or revealed no remarkable effect on cell survival. Simultaneous treatment of cells with taxanes and flavonoids baicalein, chrysin, luteolin, fisetin, quercetin, genistein or daidzein did not lead to any change in chemotherapy-induced cytotoxicity. However, simultaneous exposure of cells to hesperetin and taxanes resulted in 9.8- and 13.1-fold reduction in cytotoxicity of docetaxel and cabazitaxel, respectively.

CONCLUSION

Flavonoid hesperetin remarkably suppressed the cytotoxic efficacy of taxanes in prostate cancer cells. Therefore, caution is required from prostate cancer patients who take hesperetin-containing oral supplements.

摘要

背景/目的:超过半数的前列腺癌患者除了接受传统治疗外,还会使用某种补充药物,包括富含类黄酮的产品。然而,关于类黄酮与细胞毒性化疗药物联合作用的知识仍然相当匮乏。因此,本研究旨在评估类黄酮在人晚期前列腺癌细胞中的细胞毒性活性及其与紫杉烷类药物的相互作用。

材料与方法

采用MTT比色法,在人转移性前列腺癌细胞系PPC-1中研究了不同类黄酮的细胞毒性及其对多西他赛和卡巴他赛疗效的影响。

结果

两种紫杉烷类药物均能抑制PPC-1细胞的活力,其IC值处于纳摩尔范围。受试类黄酮仅在高微摩尔浓度下发挥细胞毒性活性,或对细胞存活无显著影响。用紫杉烷类药物与类黄酮黄芩素、白杨素、木犀草素、非瑟酮、槲皮素、染料木黄酮或大豆苷元同时处理细胞,并未导致化疗诱导的细胞毒性发生任何变化。然而,细胞同时暴露于橙皮素和紫杉烷类药物时,多西他赛和卡巴他赛的细胞毒性分别降低了9.8倍和13.1倍。

结论

类黄酮橙皮素显著抑制紫杉烷类药物在前列腺癌细胞中的细胞毒性疗效。因此,服用含橙皮素口服补充剂的前列腺癌患者需谨慎。

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