Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

Liu-Jing Cao; Li-Ya Liu; You-Qin Chen; Yu-Ying Han; Li-Hui Wei; Meng-Ying Yao; Yi Fang; Mei-Zhu Wu; Ying Cheng; Thomas J Sferra; Hui-Xin Liu; Li Li; Jun Peng; A-Ling Shen

doi:10.1007/s11655-024-3709-5

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

Chin J Integr Med. 2024 Jan 13. doi: 10.1007/s11655-024-3709-5. Online ahead of print.

Authors

Liu-Jing Cao^{1

2}, Li-Ya Liu^{1

2}, You-Qin Chen³, Yu-Ying Han^{1

2}, Li-Hui Wei^{1

2

4}, Meng-Ying Yao^{1

2}, Yi Fang^{1

2

4}, Mei-Zhu Wu^{1

2}, Ying Cheng^{1

2}, Thomas J Sferra³, Hui-Xin Liu^{1

2}, Li Li⁵, Jun Peng^{1

2

4}, A-Ling Shen^{6

7

8}

Affiliations

¹ Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
² Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
³ Department of Pediatrics, Case Western Reserve University School of Medicine, UH Rainbow Babies and Children's Hospital, Cleveland, OH, 44106, USA.
⁴ Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
⁵ Department of Health Management, Fujian Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou, 000000, China.
⁶ Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. saling86@hotmail.com.
⁷ Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. saling86@hotmail.com.
⁸ Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. saling86@hotmail.com.

PMID: 38216838
DOI: 10.1007/s11655-024-3709-5

Abstract

Objective: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells.

Methods: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.

Results: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).

Conclusion: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Keywords: Chinese medicine; Pien Tze Huang; colorectal cancer; p53/p21 pathway; partner of NOB1; proliferation.