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. 2023 Mar 2;83(9):1426–1442. doi: 10.1158/0008-5472.CAN-22-3000

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©2023 The Authors; Published by the American Association for Cancer Research

This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

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Figure 6. Cystine is a major contributor to the cysteine pool in tumors. A, Analysis of the fraction labeling in cysteine, γ-glutamylcysteine, and glutathione in liver tissues (N = 9), HCC tumors (N = 9), lung tissues (N = 10), Nrf2WT LUAD tumors (N = 16), Nrf2D29H LUAD tumors (N = 10), pancreas tissues (N = 3), PDAC tumors (N = 12), and their matched serum from normal control mice for HCC (N = 6), HCC (N = 7), normal control mice for PDAC (N = 3), PDAC (N = 6), normal control mice for LUAD (N = 5), Nrf2WT LUAD (N = 8), and Nrf2D29H LUAD serum (N = 5) following infusion with 13C6-cystine. B, Total signal of glutathione in the tissues from A. C, Total signal of cysteine in the tissues from A. For A–C, data are presented as mean ± SD. N.D., not detected. D, Immunoblots of xCT, GCLC, GCLM, and GSS for each tissue. HSP90 was used for the loading control. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Cys, cysteine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine. — Cystine is a major contributor to the cysteine pool in tumors. A, Analysis of the fraction labeling in cysteine, γ-glutamylcysteine, and glutathione in liver tissues (N = 9), HCC tumors (N = 9), lung tissues (N = 10), Nrf2^WT LUAD tumors (N = 16), Nrf2^D29H LUAD tumors (N = 10), pancreas tissues (N = 3), PDAC tumors (N = 12), and their matched serum from normal control mice for HCC (N = 6), HCC (N = 7), normal control mice for PDAC (N = 3), PDAC (N = 6), normal control mice for LUAD (N = 5), Nrf2^WT LUAD (N = 8), and Nrf2^D29H LUAD serum (N = 5) following infusion with ¹³C₆-cystine. B, Total signal of glutathione in the tissues from A. C, Total signal of cysteine in the tissues from A. For A–C, data are presented as mean ± SD. N.D., not detected. D, Immunoblots of xCT, GCLC, GCLM, and GSS for each tissue. HSP90 was used for the loading control. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Cys, cysteine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine.