Cell-specific Retention and Action of Pheophorbide-based Photosensitizers in Human Lung Cancer Cells.

ABSTRACT: This study determined in primary cultures of human lung cancer cells the cell specificity of chlorin-based photosensitizers. Epithelial cells (ECs) preferentially retained 3-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and related structural variants. Tumor-associated fibroblasts (Fb) differ from EC by a higher efflux rate of HPPH. Immunoblot analyses indicated dimerization of STAT3 as a reliable biomarker of the photoreaction. Compared to mitochondria/ER-localized photoreaction by HPPH, the photoreaction by lysosomally targeted HPPH-lactose showed a trend toward lower STAT3 cross-linking. Lethal consequence of the photoreaction differed between EC and Fb with the latter cells being more resistant. A survey of lung tumor cases indicated a large quantitative range by which EC retains HPPH. The specificity of HPPH retention defined in vitro could be confirmed in vivo in selected cases grown as xenografts. HPPH retention as a function of the tetrapyrrole structure was evaluated by altering side groups on the porphyrin macrocycle. The presence or absence of a carboxylic acid at position 17² proved to be critical. A benzyl group at position 20 enhanced retention in a subset of cancer cells with low HPPH binding. This study indicated experimental tools that are potentially effective in defining the photosensitizer preference and application for individual patient's cancer lesions.

SUBMITTER: Tracy EC 

PROVIDER: S-EPMC6496943 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature