Issa Mark E, Cuendet Muriel
School of Pharmaceutical Sciences , University of Geneva , University of Lausanne , Rue Michel Servet 1 , CH-1211 Geneva 4 , Switzerland . Email:
Medchemcomm. 2016 Nov 17;8(1):112-121. doi: 10.1039/c6md00410e. eCollection 2017 Jan 1.
Multiple myeloma (MM) remains an incurable malignancy despite the development of novel therapeutics. This is believed to be due to a subset of rare chemotherapy-resistant cancer stem cells (CSCs). Differentiation therapy represents one strategy aimed at reducing the stemness of CSCs. The anticancer effect of withaferin A (WFA) was studied in MM-CSCs and RPMI 8226 MM tumoral plasma cells (RPMIs). WFA exhibited growth inhibitory effects in both MM-CSCs and RPMIs, with IC values of 649 and 224 nM, respectively. WFA also induced a G cell cycle arrest, as well as cell death and apoptosis. Although, WFA did not exhibit a direct anti-migratory effect, a remarkable morphological change was observed in MM-CSCs in response to WFA treatment. Using qPCR gene expression analyses, WFA caused a reduction in stemness markers, and a promotion of differentiation markers in MM-CSCs. These results warrant further investigation of WFA in relevant MM animal models.
尽管有新型疗法的发展，多发性骨髓瘤（MM）仍然是一种无法治愈的恶性肿瘤。这被认为是由于一小部分罕见的化疗耐药癌症干细胞（CSCs）所致。分化疗法是旨在降低CSCs干性的一种策略。研究了白英素A（WFA）在MM-CSCs和RPMI 8226 MM肿瘤浆细胞（RPMIs）中的抗癌作用。WFA在MM-CSCs和RPMIs中均表现出生长抑制作用，IC值分别为649和224 nM。WFA还诱导了G期细胞周期停滞以及细胞死亡和凋亡。虽然WFA没有表现出直接的抗迁移作用，但在WFA处理的MM-CSCs中观察到了显著的形态变化。使用qPCR基因表达分析，WFA导致MM-CSCs中干性标志物减少，分化标志物增加。这些结果值得在相关的MM动物模型中进一步研究WFA。
