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High aldehyde dehydrogenase activity does not protect colon cancer cells against TPCS2a-sensitized photokilling.
Photochemical & Photobiological Sciences ( IF 2.7 ) Pub Date : 2020-02-28 , DOI: 10.1039/c9pp00453j Judith Jing Wen Wong 1 , Pål Kristian Selbo 1
Photochemical & Photobiological Sciences ( IF 2.7 ) Pub Date : 2020-02-28 , DOI: 10.1039/c9pp00453j Judith Jing Wen Wong 1 , Pål Kristian Selbo 1
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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: ALDHbright, ALDHdim and unsorted (bulk) and treated with chemo-, radio- or photodynamic therapy (PDT) using the clinical relevant photosensitizer disulfonated tetraphenyl chlorin (TPCS2a/fimaporfin). Here we show that there is no difference in cytotoxic responses to TPCS2a-PDT in ALHDbright, ALDHdim or bulk cancer cells. Likewise, both 5-FU and oxaliplatin chemotherapy efficacy was not reduced in ALDHbright as compared to ALDHdim cancer cells. However, we found that ALHDbright HT-29 cells are significantly less sensitive to ionizing radiation compared to ALDHdim cells. This study demonstrates that the cytotoxic response to PDT (using TPCS2a as photosensitizer) is independent of ALDH activity in HT-29 cancer cells. Our results further strengthen the use of TPCS2a to target CSCs.
中文翻译：
高醛脱氢酶活性不能保护结肠癌细胞免受TPCS2a致敏的光杀死作用。
醛脱氢酶（ALDH）是在癌症干细胞（CSC）中上调的解毒酶，可能引起化学和电离辐射（IR）治疗耐药性。通过使用ALDEFLUOR分析，将CD133 +人结肠癌细胞HT-29分为三类：ALDHbright，ALDHdim和未分选（大量），并使用化学相关的光敏剂经化学，放射或光动力疗法（PDT）处理四苯基二氢卟酚（TPCS2a / fimaporfin）。在这里，我们显示在ALHDbright，ALDHdim或大量癌细胞中，对TPCS2a-PDT的细胞毒性反应没有差异。同样，与ALDHdim癌细胞相比，ALDHbright中5-FU和奥沙利铂的化疗效果均未降低。但是，我们发现ALHDbright HT-29细胞与ALDHdim细胞相比，对电离辐射的敏感性显着降低。这项研究表明，对PDT的细胞毒性反应（使用TPCS2a作为光敏剂）独立于HT-29癌细胞中的ALDH活性。我们的结果进一步加强了针对目标CSC的TPCS2a的使用。
更新日期：2020-03-19
中文翻译：
高醛脱氢酶活性不能保护结肠癌细胞免受TPCS2a致敏的光杀死作用。
醛脱氢酶（ALDH）是在癌症干细胞（CSC）中上调的解毒酶，可能引起化学和电离辐射（IR）治疗耐药性。通过使用ALDEFLUOR分析，将CD133 +人结肠癌细胞HT-29分为三类：ALDHbright，ALDHdim和未分选（大量），并使用化学相关的光敏剂经化学，放射或光动力疗法（PDT）处理四苯基二氢卟酚（TPCS2a / fimaporfin）。在这里，我们显示在ALHDbright，ALDHdim或大量癌细胞中，对TPCS2a-PDT的细胞毒性反应没有差异。同样，与ALDHdim癌细胞相比，ALDHbright中5-FU和奥沙利铂的化疗效果均未降低。但是，我们发现ALHDbright HT-29细胞与ALDHdim细胞相比，对电离辐射的敏感性显着降低。这项研究表明，对PDT的细胞毒性反应（使用TPCS2a作为光敏剂）独立于HT-29癌细胞中的ALDH活性。我们的结果进一步加强了针对目标CSC的TPCS2a的使用。
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