Augmentation of Docetaxel-Induced Cytotoxicity in Human PC-3 Androgen-Independent Prostate Cancer Cells by Combination With Four Natural Apoptosis-Inducing Anticancer Compounds.
Augmentation of Docetaxel-Induced Cytotoxicity in Human PC-3 Androgen-Independent Prostate Cancer Cells by Combination With Four Natural Apoptosis-Inducing Anticancer Compounds.
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DOI：
10.1177/1934578x231175323
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发表时间：
2023-05
影响因子：
1.8
通讯作者：
Mansour, Mahmoud M.
中科院分区：
文献类型：
--
作者：
Ahmed, Inass A.;Hafiz, Saly;van Ginkel, Sabrina;Pondugula, Satyanarayana R.;Abdelhaffez, Azza S.;Sayyed, Hayam G.;Abd El-Aziz, Ebtihal A.;Mansour, Mahmoud M.
多西他赛（DTX）是治疗转移性去势抵抗性前列腺癌的首选。然而，发展耐药性是实现有效治疗的重大挑战。本研究使用PC-3雄激素抵抗的人前列腺癌细胞评估了四种天然化合物（calebin A、3′-hydroxypterostilbene、hispolon和tetrahydrocurcumin）对DTX的抗癌和协同作用。我们利用CellTiter-Glo®发光细胞活力测定和人PC-3雄激素非依赖性前列腺癌细胞来确定四种化合物单独和与DTX组合的抗增殖作用。使用正常永生化人前列腺上皮细胞（RWPE-1）平行测试对正常人前列腺上皮细胞的细胞毒性。我们使用细胞成像和定量caspase-3活性来确定这些化合物是否诱导细胞凋亡。我们还使用比色测定法测量了每种药物抑制TNF-α诱导的NF-kB的能力。我们的研究结果表明，所有四种天然化合物显着增加的毒性DTX雄激素耐药PC-3前列腺癌细胞的IC 50。有趣的是，当单独使用时，四种化合物中的每一种对PC-3的细胞毒活性均高于DTX。从机制上讲，这些化合物诱导细胞凋亡，我们证实了细胞成像和半胱天冬酶-3比色测定。此外，当单独使用或与DTX组合使用时，四种测试化合物抑制TNF-α诱导的NF-kB产生。更重要的是，对正常永生化人前列腺上皮细胞的细胞毒性效应极小且不显著，表明具有前列腺癌特异性效应。总之，DTX与四种测试化合物的组合可以有效地增强DTX的抗前列腺癌活性。这种组合具有降低DTX有效浓度的附加值。我们推测calebin A、3′-hydroxypterostilbene、hispolon和tetrahydrocurcumin都是很好的候选药物，单独使用时产生显著的抗增殖活性，并协同增强DTX的抗癌作用。进一步的体内研究，需要使用前列腺癌的动物模型，以确认我们的体外研究结果。
Docetaxel (DTX) is the treatment of choice for metastatic castration-resistant prostate cancer. However, developing drug resistance is a significant challenge for achieving effective therapy. This study evaluated the anticancer and synergistic effects on DTX of four natural compounds (calebin A, 3′-hydroxypterostilbene, hispolon, and tetrahydrocurcumin) using PC-3 androgen-resistant human prostate cancer cells. We utilized the CellTiter-Glo® luminescent cell viability assay and human PC-3 androgen-independent prostate cancer cells to determine the antiproliferative effects of the four compounds alone and combined with DTX. Cytotoxicity to normal human prostate epithelial cells was tested in parallel using normal immortalized human prostate epithelial cells (RWPE-1). We used cell imaging and quantitative caspase-3 activity to determine whether these compounds induce apoptosis. We also measured the capacity of each drug to inhibit TNF-α-induced NF-kB using a colorimetric assay. Our results showed that all four natural compounds significantly augmented the toxicity of DTX to androgen-resistant PC-3 prostate cancer cells at IC50. Interestingly, when used alone, each of the four compounds had a higher cytotoxic activity to PC-3 than DTX. Mechanistically, these compounds induced apoptosis, which we confirmed by cell imaging and caspase-3 colorimetric assays. Further, when used either alone or combined with DTX, the four test compounds inhibited TNF-α-induced NF-kB production. More significantly, the cytotoxic effects on normal immortalized human prostate epithelial cells were minimal and non-significant, suggesting prostate cancer-specific effects. In conclusion, the combination of DTX with the four test compounds could effectively enhance the anti-prostate cancer activity of DTX. This combination has the added value of reducing the DTX effective concentration. We surmise that calebin A, 3′-hydroxypterostilbene, hispolon, and tetrahydrocurcumin were all excellent drug candidates that produced significant antiproliferative activity when used alone and synergistically enhanced the anticancer effect of DTX. Further in vivo studies using animal models of prostate cancer are needed to confirm our in vitro findings.
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影响因子：
3.3
作者：
Han X;Deng S;Wang N;Liu Y;Yang X
通讯作者：
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