Spectroscopic investigation of the interaction between G-quadruplex of KRAS promoter sequence and three isoquinoline alkaloids

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 171; pp. 287 - 296
• Main Authors: Wen, Li-Na, Xie, Meng-Xia
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.01.2017
• Subjects: Alkaloids - chemistry; Alkaloids - metabolism; Base Sequence; Binding mode; Cell Line, Tumor; Cell Proliferation; Circular Dichroism; Fluorescence Polarization; G-Quadruplexes; Humans; Isoquinoline alkaloids; Isoquinolines - chemistry; Isoquinolines - metabolism; KRAS promoter quadruplex; Potassium Iodide - chemistry; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Spectrometry, Fluorescence; Spectroscopy; Structure-Activity Relationship; Temperature; JTZ; CD; Spectroscopy; BBR; Binding mode; KRAS promoter quadruplex; NHE; Isoquinoline alkaloids; SGR
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2016.08.013

KRAS promoter can form G-quadruplex structure and regulate gene transcription. The drugs which can bind with G-quadruplex of KRAS promoter may be potential remedy for treatment of cancers associated with KRAS mutation. The interaction mechanism between the G-quadruplex of KRAS promoter and three isoquinoline alkaloids (jatrorrhizine, berberine and sanguinarine) has been investigated by UV-visible, fluorescence and circular dichroism spectroscopic methods. The results showed that the three alkaloids can form complexes with G-quadruplex KRAS promoter with the molecular ratio of 1:1, and the binding constants were (0.90±0.16)×106Lmol−1, (0.93±0.21)×106Lmol−1 and (1.16±0.45)×106Lmol−1 for jatrorrhizine, berberine and sanguinarine. The absorption spectra, KI quenching and fluorescence anisotropy and polarization studies suggested jatrorrhizine and berberine interacted with G-quadruplex by not only end-stacking binding mode but also grooves or loops binding mode, while sanguinarine by end-stacking binding mode. Sanguinarine was more beneficial to maintain the stability and parallel conformation of KRAS promoter G-quadruplex. MTT assay was performed to evaluate antiproliferation effects of the three isoquinoline alkaloids on SW620 cells, and the antiproliferation effects of the three alkaloids were sanguinarine > berberine > jatrorrhizine. All the three alkaloids can bind with KRAS promoter G-quadruplex, and sanguinarine had the better binding property and antiproliferation effects on SW620 cells. The results obtained are meaningful to explore potential reagents targeting the parallel G-quadruplex structure of KRAS promoter for gene theraphy of colorectal carcinomas. [Display omitted] •Binding modes of three alkaloids with KRAS G-quadruplex were comparatively probed by different spectroscopic methods.•Sanguinarine was more beneficial to maintain the parallel G-quadruplex structure.•Sanguinarine had a better binding capacity and a more effective antiproliferation activity on SW620 cells.•Binding property with KRAS G-quadruplex and antiproliferation effects of alkaloids were related to molecular structures.