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Hedyotis diffusae Herba-Andrographis Herba inhibits the cellular proliferation of nasopharyngeal carcinoma and triggers DNA damage through activation of p53 and p21

Cancer Gene Therapy volume 29, pages 973–983 (2022)Cite this article

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A Correction to this article was published on 20 May 2022

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Abstract

Dysregulation of the cell cycle and the resulting aberrant cellular proliferation has been highlighted as a hallmark of cancer. Certain traditional Chinese medicines can inhibit cancer growth by inducing cell cycle arrest. In this study we explore the effect of Hedyotis diffusae Herba-Andrographis Herba on the cell cycle of nasopharyngeal carcinoma (NPC). Hedyotis diffusae Herba-Andrographis Herba-containing serum was prepared and then added to the cell culture medium. BrdU, comet, and FUCCI assays, western blot analysis and flow cytometry analysis revealed that Hedyotis diffusae Herba-Andrographis Herba treatment significantly alters cell proliferation, DNA damage, and cell cycle distribution. Xenograft mouse model experiments were performed, confirming these in vitro findings in vivo. Treatment with Hedyotis diffusae Herba-Andrographis Herba inhibited cell proliferation, promoted DNA damage, and arrested NPC cells progression from G1 to S phase. Further examination of the underlying molecular mechanisms revealed that treatment with Hedyotis diffusae Herba-Andrographis Herba increased the expression of p53 and p21, while reducing that of CCND1, Phospho-Rb, E2F1, γH2AX, and Ki-67 both in vivo and in vitro. Conversely, the inhibition of p53 and p21 could abolish the promoting effect of Hedyotis diffusae Herba-Andrographis Herba on the NPC cell cycle arrest at the G1 phase, contributing to the proliferation of NPC cells. Hedyotis diffusae Herba-Andrographis Herba suppressed the tumor growth in vivo. Overall, these findings suggest that Hedyotis Diffusae Herba-Andrographis prevent the progression of NPC by inducing NPC cell cycle arrest at the G1 phase through a p53/p21-dependent mechanism, providing a novel potential therapeutic treatment against NPC.

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Fig. 1: Hedyotis diffusae Herba-Andrographis Herba inhibits NPC cell proliferation.
Fig. 2: Hedyotis diffusae Herba-Andrographis Herba administration suppresses the tumorigenicity of NPC cells in vivo.
Fig. 3: Administration of Hedyotis diffusae Herba-Andrographis Herba facilitates DNA damage in C666-1 and SUNE-1 cells.
Fig. 4: Hedyotis diffusae Herba-Andrographis Herba treatment inhibits cell cycle progression in C666-1 and SUNE-1 cells.
Fig. 5: Hedyotis diffusae Herba-Andrographis Herba treatment blocks cell cycle progression in vivo.
Fig. 6: Hedyotis diffusae Herba-Andrographis Herba treatment restrains cell cycle progression resulting in decreased viability and proliferation of C666-1 and SUNE-1 cells by altering the p53/p21/CCND1 regulatory axis.
Fig. 7: Schematic diagram summarizing the effects of Hedyotis diffusae Herba-Andrographis Herba on cell cycle progression and proliferation of NPC.

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Funding

This study was supported by the National Twelfth Five-Year Support Plan (No. 2015BAI04B00), and National Natural Science Foundation of China (No. 81273985 & 81403440).

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  1. These authors contributed equally: Zhiqing Liu, Shan Mu.

Authors and Affiliations

  1. Department of Otolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China

    Zhiqing Liu, Shan Mu, Sha Li, Jiao Liang, Zuo Yang, Jiongke Li, Qinwei Fu, Xiaodong Chen, Lingyan Ding, Rui Han, Qinxiu Zhang & Hui Xie

  2. Department of Traditional Chinese Medicine, Hi-tech Zhonghe Community Health Service Center, Chengdu, P. R. China

    Yuanyuan Deng

  3. Department of Ophthalmology and Otorhinolaryngology, Sichuan Integrative Medicine Hospital, Chengdu, P. R. China

    Liu Cao

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Contributions

ZL and SM conceived and designed research. SL and JL performed experiments. YD and ZY interpreted results of experiments. JL and LC analyzed data. QF and XC prepared figures. LD and RH drafted paper. QZ and HX edited and revised manuscript. All authors read and approved final version of manuscript.

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Correspondence to Qinxiu Zhang or Hui Xie.

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The experiments involving animals were performed under approval of the Institutional Animal Care and Use Committee of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine and in compliance with the recommendations in the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. All efforts were made to minimize the number and suffering of the animals.

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Liu, Z., Mu, S., Li, S. et al. Hedyotis diffusae Herba-Andrographis Herba inhibits the cellular proliferation of nasopharyngeal carcinoma and triggers DNA damage through activation of p53 and p21. Cancer Gene Ther 29, 973–983 (2022). https://doi.org/10.1038/s41417-021-00385-7

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