High aldehyde dehydrogenase activity does not protect colon cancer cells against TPCS_2a-sensitized photokilling

Aldehyde dehydrogenases (ALDH) are detoxifying enzymes that are upregulated in cancer stem cells (CSCs) and may cause chemo- and ionizing radiation (IR) therapy resistance. By using the ALDEFLUOR assay, CD133 + human colon cancer cells HT-29, were FACSorted into three populations: ALDH^bright, ALDH^dim and unsorted (bulk) and treated with chemo-, radio- or photodynamic therapy (PDT) using the clinical relevant photosensitizer disulfonated tetraphenyl chlorin (TPCS_2a/fimaporfin). Here we show that there is no difference in cytotoxic responses to TPCS_2a-PDT in ALHD^bright, ALDH^dim or bulk cancer cells. Likewise, both 5-FU and oxaliplatin chemotherapy efficacy was not reduced in ALDH^bright as compared to ALDH^dim cancer cells. However, we found that ALHD^bright HT-29 cells are significantly less sensitive to ionizing radiation compared to ALDH^dim cells. This study demonstrates that the cytotoxic response to PDT (using TPCS_2a as photosensitizer) is independent of ALDH activity in HT-29 cancer cells. Our results further strengthen the use of TPCS_2a to target CSCs.