Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park 2006, South Africa.
Photodiagnosis Photodyn Ther. 2012 Sep;9(3):215-24. doi: 10.1016/j.pdpdt.2011.12.008. Epub 2012 Jan 14.
Cancer cells possess an innate resistance to inducers of the death program. Novel phthalocyanines with improved physiochemical properties harbor the potential for use in photodynamic therapy (PDT); a rising treatment alternative preferred for its mostly asymptomatic application and unique mechanism of action.
This study aimed to determine whether in vitro PDT with two new metallo-phthalocyanines (metallo-Pcs), AlPcSmix and GePcSmix, are similarly effective in overcoming resistance to cell death in MCF-7 cells with a brief comparison to an established chemotherapeutic agent, etoposide. Optimum induction of cell death in these cancer cells was initially determined via measurement of cellular respiration and energy production levels. Indications of cytotoxicity and cell stress were evaluated and resultant levels compared to those in cells treated with etoposide.
Initial findings report AlPcSmix is predominantly more detrimental to cellular function and homeostasis when excited via red light irradiation of 15 J/cm(2). It appears GePcSmix requires higher dosage administrations to achieve similar responses within identical populations. However, due to the mechanism of PDT application, our findings indicate a greater toxic effect with both phthalocyanines when compared to etoposide of higher dosage within MCF-7 cells.
Both phthalocyanines, despite similarity in structure, indicate induction of different cell death response pathways based on their toxicity potential. These therefore show great promise as potential PDT agents for the treatment of cancer.
癌细胞具有对死亡程序诱导剂的固有抗性。具有改进的物理化学性质的新型酞菁化合物具有用于光动力疗法(PDT)的潜力;这种治疗方法越来越受欢迎,因为它主要是无症状应用,并且具有独特的作用机制。
本研究旨在确定两种新型金属酞菁(金属 Pc),AlPcSmix 和 GePcSmix,通过体外 PDT 是否同样有效地克服 MCF-7 细胞对细胞死亡的抗性,并与一种已建立的化疗药物依托泊苷进行简短比较。最初通过测量细胞呼吸和能量产生水平来确定这些癌细胞中最佳的细胞死亡诱导。评估细胞毒性和细胞应激的迹象,并将结果与用依托泊苷处理的细胞进行比较。
初步研究结果报告称,当用 15 J/cm(2)的红光照射激发时,AlPcSmix 对细胞功能和内稳态的损害主要更大。似乎 GePcSmix 需要更高的剂量给药才能在相同的群体中达到类似的反应。然而,由于 PDT 应用的机制,我们的研究结果表明,与 MCF-7 细胞中更高剂量的依托泊苷相比,两种酞菁的毒性作用更大。
尽管结构相似,但两种酞菁都表明基于其毒性潜力诱导不同的细胞死亡反应途径。因此,它们作为癌症治疗的潜在 PDT 药物具有很大的潜力。