Open Access

Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells

  • Authors:
    • Hai-Qun Dong
    • Shi-Jing Liang
    • Yu-Ling Xu
    • Yi Dai
    • Na Sun
    • Dong-Hong Deng
    • Peng Cheng
  • View Affiliations

  • Published online on: August 17, 2022     https://doi.org/10.3892/ijo.2022.5409
  • Article Number: 119
  • Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Leukemia is a fatal hematopoietic disorder with a poor prognosis. Drug resistance is inevitable after the long‑term use of chemotherapeutic agents. Liproxstatin‑1, commonly known as a ferroptosis inhibitor, has never been reported to have anticancer effects. In the present study, the antileukemic role of liproxstatin‑1 in K562 leukemia cells was investigated. Liproxstatin‑1 inhibited K562 cell proliferation in a dose‑ and time‑dependent manner. RNA sequencing revealed several pathways that were affected by liproxstatin‑1, such as the G1/S transition of the mitotic cell cycle and extrinsic or intrinsic apoptotic signaling pathways. The results of flow cytometry indicated that liproxstatin‑1 arrests the cell cycle at the G1 phase, and even at the G2/M phase. p21WAF1/CIP1, a cyclin‑dependent kinase inhibitor, was upregulated. It was also determined that liproxstatin‑1 induced BAX and TNF‑α expression, which was accompanied by cleavage of caspase‑3 and PARP. The caspase‑3‑specific inhibitor z‑DEVD‑FMK rescued some of the apoptotic cells. Interestingly, K562 cells were characterized by swelling and plasma membrane rupture when treated with a high concentration of liproxstatin‑1, which was inconsistent with the typical apoptotic appearance. Thus, it was hypothesized that apoptosis‑mediated pyroptosis occurs during liproxstatin‑1‑induced cell death. The expression of the hallmark of pyroptosis, the cleaved N‑terminal GSDME, increased. Additionally, it was observed that endoplasmic reticulum stress and autophagy were involved in liproxstatin‑1‑induced cell death. Collectively, liproxstatin‑1 induced cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 leukemia cells, which provides new hope for the treatment of leukemia.
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October-2022
Volume 61 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Dong H, Liang S, Xu Y, Dai Y, Sun N, Deng D and Cheng P: Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells. Int J Oncol 61: 119, 2022
APA
Dong, H., Liang, S., Xu, Y., Dai, Y., Sun, N., Deng, D., & Cheng, P. (2022). Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells. International Journal of Oncology, 61, 119. https://doi.org/10.3892/ijo.2022.5409
MLA
Dong, H., Liang, S., Xu, Y., Dai, Y., Sun, N., Deng, D., Cheng, P."Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells". International Journal of Oncology 61.4 (2022): 119.
Chicago
Dong, H., Liang, S., Xu, Y., Dai, Y., Sun, N., Deng, D., Cheng, P."Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells". International Journal of Oncology 61, no. 4 (2022): 119. https://doi.org/10.3892/ijo.2022.5409