1. Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China. 2. Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. 3. Public Service Platform of Tumor organoids Technology, 283 Tongzipo Road, Changsha, 410013, Hunan, China. *The authors contribute equally to the work.
✉ Corresponding authors: Yujuan Zhou or Qianjin Liao or Yingrui Shi, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China. Tel: 86-731-88651681; Fax: 86-731-88651999; Email: yujany_zhoucom or liaoqianjinorg.cn or shiyingruiorg.cn.More
Citation:
Xia L, Lin J, Peng M, Jiang X, Peng Q, Cui S, Zhang W, Li S, Wang J, Oyang L, Tan S, Hu Z, Wu N, Tang Y, Luo X, Ren Z, Shi Y, Liao Q, Zhou Y. Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination. Int J Biol Sci 2024; 20(4):1125-1141. doi:10.7150/ijbs.91206. https://www.ijbs.com/v20p1125.htm
Previous studies have demonstrated that diallyl disulfide (DADS) exhibits potent anti-tumor activity. However, the pharmacological actions of DADS in inhibiting the growth of colorectal cancer (CRC) cells have not been clarified. Herein, we show that DADS treatment impairs the activation of the pentose phosphate pathway (PPP) to decrease PRPP (5-phosphate ribose-1-pyrophosphate) production, enhancing DNA damage and cell apoptosis, and inhibiting the growth of CRC cells. Mechanistically, DADS treatment promoted POU2F1 K48-linked ubiquitination and degradation by attenuating the PI3K/AKT signaling to up-regulate TRIM21 expression in CRC cells. Evidently, TRIM21 interacted with POU2F1, and induced the K272 ubiquitination of POU2F1. The effects of DADS on the enhanced K272 ubiquitination of POU2F1, the PPP flux, PRPP production, DNA damage and cell apoptosis as well as the growth of CRC tumors in vivo were significantly mitigated by TRIM21 silencing or activating the PI3K signaling in CRC cells. Conversely, the effects of DADS were enhanced by TRIM21 over-expression or inhibiting the PI3K/AKT signaling in CRC cells. Collectively, our findings reveal a novel mechanism by which DADS suppresses the growth of CRC by promoting POU2F1 ubiquitination, and may aid in design of novel therapeutic intervention of CRC.
Keywords: diallyl disulfide, the pentose phosphate pathway, DNA damage, apoptosis, POU2F1 ubiquitination
Citation styles
APA
Xia, L., Lin, J., Peng, M., Jiang, X., Peng, Q., Cui, S., Zhang, W., Li, S., Wang, J., Oyang, L., Tan, S., Hu, Z., Wu, N., Tang, Y., Luo, X., Ren, Z., Shi, Y., Liao, Q., Zhou, Y. (2024). Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination. International Journal of Biological Sciences, 20(4), 1125-1141. https://doi.org/10.7150/ijbs.91206.
ACS
Xia, L.; Lin, J.; Peng, M.; Jiang, X.; Peng, Q.; Cui, S.; Zhang, W.; Li, S.; Wang, J.; Oyang, L.; Tan, S.; Hu, Z.; Wu, N.; Tang, Y.; Luo, X.; Ren, Z.; Shi, Y.; Liao, Q.; Zhou, Y. Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination. Int. J. Biol. Sci. 2024, 20 (4), 1125-1141. DOI: 10.7150/ijbs.91206.
NLM
Xia L, Lin J, Peng M, Jiang X, Peng Q, Cui S, Zhang W, Li S, Wang J, Oyang L, Tan S, Hu Z, Wu N, Tang Y, Luo X, Ren Z, Shi Y, Liao Q, Zhou Y. Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination. Int J Biol Sci 2024; 20(4):1125-1141. doi:10.7150/ijbs.91206. https://www.ijbs.com/v20p1125.htm
CSE
Xia L, Lin J, Peng M, Jiang X, Peng Q, Cui S, Zhang W, Li S, Wang J, Oyang L, Tan S, Hu Z, Wu N, Tang Y, Luo X, Ren Z, Shi Y, Liao Q, Zhou Y. 2024. Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination. Int J Biol Sci. 20(4):1125-1141.
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