Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India.
KPC Medical College, Jadavpur, Kolkata 700032, India.
J Photochem Photobiol B. 2019 May;194:140-148. doi: 10.1016/j.jphotobiol.2019.03.011. Epub 2019 Mar 21.
Previously, we reported that coralyne and UVA combination sensitized a wide range of human carcinoma cells regardless of their p53 status. The coralyne induced photosensitization of cancer cells may be clinically attractive, as mutation in the p53 gene is prevalent in many types of tumors. Coralyne mediated photosensitization of cancer cells is attributable to its ability to cause extensive DNA single strand breaks (SSB). However, the precise mechanism of coralyne induced DNA photo-damage is not yet known. The present study was aimed to understand the hitherto unknown mechanism of the coralyne-induced DNA photo-cleavage process. To this end, we compared the DNA photo-nicking properties of berberine, jatrorrhizine and coralyne, and deciphered involvement of the photochemical processes in the photo-nuclease action of coralyne using absorption and electron spin resonance spectroscopy, high performance liquid chromatography and mass spectroscopy (MS) techniques in conjunction with relevant in vitro studies with plasmid DNA. In association with UVA, coralyne, but not berberine and jatrorrhizine induced significant nicking of plasmid DNA via an O-independent photo-chemical process. The Job's plot of our spectrophotometric data suggested that one coralyne molecule remains intercalated with two DNA base pairs (i. e., 1:2) and starts forming aggregates beyond this molar ratio. The DNA photo-nicking by the combination of coralyne and UVA (designated as CUVA) was primarily caused by the coralyne aggregates without any significant contribution from the DNA-intercalated coralyne monomer.
先前，我们报道了珊瑚诺林和 UVA 联合敏化了广泛的人类癌细胞，而不管其 p53 状态如何。珊瑚诺林诱导癌细胞的光敏化可能在临床上具有吸引力，因为 p53 基因的突变在许多类型的肿瘤中很常见。珊瑚诺林介导的癌细胞光敏化归因于其引起广泛 DNA 单链断裂（SSB）的能力。然而，珊瑚诺林诱导的 DNA 光损伤的确切机制尚不清楚。本研究旨在了解珊瑚诺林诱导的 DNA 光断裂过程的未知机制。为此，我们比较了小檗碱、小檗胺和珊瑚诺林的 DNA 光切刻特性，并通过吸收和电子自旋共振光谱、高效液相色谱和质谱（MS）技术结合与质粒 DNA 的相关体外研究，解析了光化学过程在珊瑚诺林光核酸酶作用中的参与。与 UVA 联合使用时，珊瑚诺林而非小檗碱和小檗胺通过 O 独立的光化学过程诱导质粒 DNA 发生显著的切口。我们的分光光度数据的 Job 图表明，一个珊瑚诺林分子与两个 DNA 碱基对（即 1:2）保持嵌入，并且超过该摩尔比开始形成聚集体。珊瑚诺林和 UVA 的组合（称为 CUVA）对 DNA 的光切刻主要是由珊瑚诺林聚集体引起的，而 DNA 嵌入的珊瑚诺林单体没有任何显著贡献。
