Abstract
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 disulfo-nated 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.
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S. S. Dinavahi, C. G. Bazewicz, R. Gowda and G. P. Robertson, Aldehyde Dehydrogenase Inhibitors for Cancer Therapeutics, Trends Pharmacol. Sci., 2019, 40(10), 774–789.
C. Ginestier, M. H. Hur, E. Charafe-Jauffret, F. Monville, J. Dutcher, M. Brown, et al., ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome, Cell Stem Cell, 2007, 1(5), 555–567.
E. H. Huang, M. J. Hynes, T. Zhang, C. Ginestier, G. Dontu, H. Appelman, et al., Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis, Cancer Res., 2009, 69(8), 3382–3389.
E. Batlle and H. Clevers, Cancer stem cells revisited, Nat. Med., 2017, 23(10), 1124–1134.
A. A. Sultan, W. Jerjes, K. Berg, A. Hogset, C. A. Mosse, R. Hamoudi, et al., Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleo-mycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial, Lancet Oncol., 2016, 17(9), 1217–1229.
P. K. Selbo, A. Weyergang, A. Hogset, O. J. Norum, M. B. Berstad, M. Vikdal, et al., Photochemical internaliz-ation provides time- and space-controlled endolysosomal escape of therapeutic molecules, J. Controlled Release, 2010, 148(1), 2–12.
R. W. Storms, A. P. Trujillo, J. B. Springer, L. Shah, O. M. Colvin, S. M. Ludeman, et al., Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity, Proc. Natl. Acad. Sci. U. S. A., 1999, 96(16), 9118–9123.
K. Lund, J. L. Dembinski, N. Solberg, A. Urbanucci, I. G. Mills and S. Krauss, Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment, PLoS One, 2015, 10(4), e0123684.
K. Lund, C. E. Olsen, J. J. W. Wong, P. A. Olsen, N. T. Solberg, A. Hogset, et al., 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immuno-toxin CD105-saporin, J. Exp. Clin. Cancer Res., 2017, 36(1), 187.
D. Kim, B. H. Choi, I. G. Ryoo and M. K. Kwak, High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling, Cell Death Dis., 2018, 9(9), 896.
L. Cortes-Dericks, L. Froment, R. Boesch, R. A. Schmid and G. Karoubi, Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDH(high)CD44(+) pheno-type and sphere-forming capacity, BMC Cancer, 2014, 14, 304.
G. Vassalli, Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells, Stem Cells Int., 2019, 2019, 3904645.
Y. Touil, W. Igoudjil, M. Corvaisier, A. F. Dessein, J. Vandomme, D. Monte, et al. Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis, Clin. Cancer Res., 2014, 20(4), 837–846.
Z. Kozovska, A. Patsalias, V. Bajzik, E. Durinikova, L. Demkova, S. Jargasova, et al., ALDH1A inhibition sensitizes colon cancer cells to chemotherapy, BMC Cancer, 2018, 18(1), 656.
L. Prasmickaite, B. O. Engesaeter, N. Skrbo, T. Hellenes, A. Kristian, N. K. Oliver, et al., Aldehyde dehydrogenase (ALDH) activity does not select for cells with enhanced aggressive properties in malignant melanoma, PLoS One, 2010, 5(5), e10731.
N. A. Dallas, L. Xia, F. Fan, M. J. Gray, P. Gaur, G. van Buren 2nd, et al., Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition, Cancer Res., 2009, 69(5), 1951–1957.
M. Todaro, M. P. Alea, A. B. Di Stefano, P. Cammareri, L. Vermeulen, F. Iovino, et al., Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4, Cell Stem Cell, 2007, 1(4), 389–402.
C. E. Olsen, L. H. Cheung, A. Weyergang, K. Berg, D. A. Vallera, M. G. Rosenblum, et al., Design, Characterization, and Evaluation of scFvCD133/rGelonin: A CD133-Targeting Recombinant Immunotoxin for Use in Combination with Photochemical Internalization, J. Clin. Med., 2019, 9(1), E68.
N. A. Franken, H. M. Rodermond, J. Stap, J. Haveman and C. van Bree, Clonogenic assay of cells in vitro, Nat. Protoc., 2006, 1(5), 2315–2319.
M. Cojoc, C. Peitzsch, I. Kurth, F. Trautmann, L. A. Kunz-Schughart, G. D. Telegeev, et al., Aldehyde Dehydrogenase Is Regulated by beta-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells., Cancer Res., 2015, 75(7), 1482–1494.
J. Mihatsch, M. Toulany, P. M. Bareiss, S. Grimm, C. Lengerke, R. Kehlbach, et al., Selection of radioresistant tumor cells and presence of ALDH1 activity in vitro, Radiother. Oncol., 2011, 99(3), 300–306.
P. Agostinis, K. Berg, K. A. Cengel, T. H. Foster, A. W. Girotti, S. O. Gollnick, et al., Photodynamic therapy of cancer: an update, Ca-Cancer J. Clin., 2011, 61(4), 250–281.
K. Berg, S. Nordstrand, P. K. Selbo, D. T. Tran, E. Angell-Petersen and A. Hogset, Disulfonated tetraphenyl chlorin (TPCS2a), a novel photosensitizer developed for clinical utilization of photochemical internalization, Photochem. Photobiol. Sci., 2011, 10(10), 1637–1651.
J. L. Merlin, S. Azzi, D. Lignon, C. Ramacci, N. Zeghari and F. Guillemin, MTT assays allow quick and reliable measurement of the response of human tumour cells to photo-dynamic therapy, Eur. J. Cancer, 1992, 28A(8-9), 1452–1458.
W. L. Yip, A. Weyergang, K. Berg, H. H. Tonnesen and P. K. Selbo, Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization in EGFR-positive cancer cells, Mol. Pharmacol., 2007, 4(2), 241–251.
P. K. Selbo, A. Weyergang, A. Bonsted, S. G. Bown and K. Berg, Photochemical internalization of therapeutic macromolecular agents: a novel strategy to kill multidrug-resistant cancer cells, J. Pharmacol. Exp. Ther., 2006, 319(2), 604–612.
P. K. Selbo, A. Weyergang, M. S. Eng, M. Bostad, G. M. Maelandsmo, A. Hogset, et al., Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug, J. Controlled Release, 2012, 159(2), 197–203.
C. E. Olsen, K. Berg, P. K. Selbo and A. Weyergang, Circumvention of resistance to photodynamic therapy in doxorubicin-resistant sarcoma by photochemical internaliz-ation of gelonin, Free Radical Biol. Med., 2013, 65, 1300–1309.
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Wong, J.J.W., Selbo, P.K. High aldehyde dehydrogenase activity does not protect colon cancer cells against TPCS2a-sensi-tized photokilling. Photochem Photobiol Sci 19, 308–312 (2020). https://doi.org/10.1039/c9pp00453j
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DOI: https://doi.org/10.1039/c9pp00453j