An ytterbium(iii) porphyrin induces endoplasmic reticulum stress and apoptosis in cancer cells: cytotoxicity and transcriptomics studiesElectronic supplementary information (ESI) available: ESI includes experimental procedures, X-ray crystallography data, electrospray-mass spectroscopy analysis of the ytterbium(iii) porphyrin complexes, UV-visible absorption spectra for monitoring the solution stability, microscopic images of the cellular morphology changes induced by 1 and the dendrogram for cl

• Main Authors: Kwong, Wai-Lun, Wai-Yin Sun, Raymond, Lok, Chun-Nam, Siu, Fung-Ming, Wong, Suk-Yu, Low, Kam-Hung, Che, Chi-Ming
• Format: Article
• Language: English
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c2sc21541a

In the literature, very few ytterbium( iii ) complexes have been reported to display promising anti-cancer activities without photoactivation or conjugation to cytotoxic counterparts/radionuclides. By employing porphyrinato ligands, which provide a rigid molecular scaffold for the ytterbium( iii ) ion and enhance cellular-uptake efficacy, we have prepared and structurally characterized a series of ytterbium( iii ) porphyrin complexes showing potent anti-cancer activities with cytotoxic IC 50 values down to the sub-micromolar range. The notable example is an ytterbium( iii ) octaethylporphyrin complex ( 1 ) which exists as a dimeric hydroxyl-bridged complex [Yb 2 (OEP) 2 (μ-OH) 2 ] (where H 2 OEP = octaethylporphyrin) in CH 2 Cl 2 solution and in solid state, and as monomeric [Yb(OEP)(DMSO)(OH)(OH 2 )] in DMSO/aqueous solution. Unlike various anti-cancer lanthanide complexes which are proposed to target cellular DNA, transcriptomics data, bioinformatics connectivity map analysis and biochemical experiments altogether indicate that 1 exerts its anti-cancer effect through apoptosis that is highly associated with the endoplasmic reticulum stress pathway. An ytterbium( iii ) octaethylporphyrin complex ( 1 ) displays anti-cancer activities with cytotoxic IC 50 values down to sub-micromolar range. Transcriptomics data and biochemical experiments indicate that 1 induces apoptosis through the endoplasmic reticulum stress pathway.