Takeuchi H, Ara G, Sausville E A, Teicher B
Dana-Farber Cancer Institute and Joint Center for Radiation Therapy, Boston, MA 02115, USA.
Cancer Chemother Pharmacol. 1998;42(6):491-6. doi: 10.1007/s002800050850.
Jasplakinolide is a novel natural product anticancer agent which acts by inducing overpolymerization of actin. The aim of the current study was to explore the activity of jasplakinolide with hyperthermia and radiation.
The response of human PC-3 and DU-145 prostate carcinoma cells and DU-145 xenografts and the response of the Lewis lung carcinoma to jasplakinolide were studied.
Jasplakinolide was cytotoxic toward human prostate carcinoma cells, DU-145, PC-3 and LNCaP in culture, killing 1 log of cells with 0.8, 0.3 and 0.07 microM of drug in 24 h, respectively. The combination of jasplakinolide and hyperthermia resulted in primarily additive cell killing by the two modalities in the three prostate carcinoma lines. In combination with radiation, jasplakinolide produced some diminution in the shoulder of the survival curve of normally oxygenated PC-3 cells and was a radiation sensitizer of hypoxic DU-145 cells and hypoxic PC-3 cells. In vivo, jasplakinolide was an active antitumor agent against the Lewis lung carcinoma and the DU-145 prostate carcinoma xenograft. Jasplakinolide was a radiation sensitizer in the Lewis lung carcinoma. Jasplakinolide was also effective against the systemic Lewis lung carcinoma, decreasing lung metastases. Lung metastases were further decreased when jasplakinolide was administered along with radiation to the subcutaneous primary tumor. In the DU-145 tumor, the effects of jasplakinolide and fractionated radiation for 1 or 2 weeks appeared to be primarily additive.
Jasplakinolide is an interesting new anticancer agent for which further study both as an anticancer agent and in combined modality regimens is warranted.
茉莉素内酯是一种新型天然产物抗癌剂，其作用机制是诱导肌动蛋白过度聚合。本研究的目的是探讨茉莉素内酯与热疗及放疗联合应用的活性。
研究了茉莉素内酯对人PC-3和DU-145前列腺癌细胞、DU-145异种移植瘤以及Lewis肺癌的反应。
茉莉素内酯对培养的人前列腺癌细胞DU-145、PC-3和LNCaP具有细胞毒性，在24小时内分别用0.8、0.3和0.07微摩尔的药物杀死1个对数级的细胞。在三种前列腺癌系中，茉莉素内酯与热疗联合主要导致两种治疗方式的相加性细胞杀伤。与放疗联合时，茉莉素内酯使正常氧合的PC-3细胞存活曲线的肩部有所降低，并且是缺氧的DU-What is the meaning of "1 log of cells" in this context? It means a tenfold reduction in the number of cells. So killing 1 log of cells means reducing the number of cells by a factor of 10.
45细胞和缺氧的PC-3细胞的放疗增敏剂。在体内，茉莉素内酯是一种对Lewis肺癌和DU-145前列腺癌异种移植瘤有效的抗肿瘤剂。茉莉素内酯在Lewis肺癌中是放疗增敏剂。茉莉素内酯对系统性Lewis肺癌也有效，可减少肺转移。当茉莉素内酯与对皮下原发性肿瘤的放疗同时给药时，肺转移进一步减少。在DU-145肿瘤中，茉莉素内酯与分割放疗1或2周的效果似乎主要是相加性的。
茉莉素内酯是一种有趣的新型抗癌剂，作为抗癌剂以及在联合治疗方案中都值得进一步研究。
