Moreira Helena, Szyjka Anna, Gąsiorowski Kazimierz
Department of Basic Medical Sciences, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, Poland.
Oncotarget. 2018 Apr 20;9(30):21211-21223. doi: 10.18632/oncotarget.25014.
Celastrol (tripterine) a pentacyclic triterpenoid extracted from the roots of Hook f., exhibits potent antioxidant and anti-inflammatory activity and also exerts important anti-cancer effects, as induction of apoptosis and lowering the level of drug resistance of several cancers. Increased level of cellular resistance to cytostatic drugs is typical for colorectal cancers, and largely determines the failure of chemotherapy for this tumor. The purpose of our research was to evaluate the chemopreventive effect of celastrol on cultures of colon cancer cells resistant to doxorubicin (LOVO/DX). With the use of flow cytometry we have shown that celastrol reduces the cell size of the SP (side population; subpopulation of cancer cells enriched with cancer stem cells), increases frequency of apoptosis and binds to Pgp protein in cell membranes inhibiting its transport function. The inhibition of the Pgp transport function has been shown to increase the accumulation of rhodamine-123 and standard cytostatic- doxorubicin in LOVO/DX cells. Our results prove that celastrol exhibits significant chemopreventive and chemosensitizing activities on drug resistant colon cancer cells. Celastrol appears to be a good candidate for adjuvant medicine that can improve the effectiveness of standard cytostatic therapy in humans.
雷公藤红素（雷公藤三萜）是从雷公藤根中提取的一种五环三萜类化合物，具有强大的抗氧化和抗炎活性，还具有重要的抗癌作用，如诱导凋亡和降低多种癌症的耐药水平。结直肠癌细胞对细胞抑制药物的耐药性增加是其典型特征，这在很大程度上决定了该肿瘤化疗的失败。我们研究的目的是评估雷公藤红素对阿霉素耐药的结肠癌细胞系（LOVO/DX）培养物的化学预防作用。通过流式细胞术，我们发现雷公藤红素可减小SP细胞（侧群细胞；富含癌症干细胞的癌细胞亚群）的细胞大小，增加凋亡频率，并与细胞膜上的Pgp蛋白结合，抑制其转运功能。Pgp转运功能的抑制已被证明可增加罗丹明-123和标准细胞抑制药物阿霉素在LOVO/DX细胞中的积累。我们的结果证明，雷公藤红素对耐药结肠癌细胞具有显著的化学预防和化学增敏活性。雷公藤红素似乎是一种辅助药物的良好候选者，可提高人类标准细胞抑制疗法的有效性。
