Maintenance of the Expression of c-FLIPL by Hsp70 to Resist Licochalcone A-Induced Anti-Colorectal Cancer Effect through ERK-Mediated Autophagy Induction

  • Front Biosci (Landmark Ed). 2023 Dec 1;28(12):325. doi: 10.31083/j.fbl2812325.
Tianpeng Li  1 ,  Ting Li  1 ,  Hongbin Zhang  2 ,  Chunyan Liu  3 ,  Min Li  4 ,  Chu Wang  4 ,  Yuanyuan Zheng  4 ,  Lihua Zhang  5 ,  Xiaoyi Long  6 ,  Shaoqing Shi  7 ,  Yun Long  8 ,  Wei Chen  1
Affiliations
  • 1. Institute of Basic Medicine and Forensic Medicine, Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, 637000 Nanchong, Sichuan, China.
  • 2. Department of Pediatric Surgery, the First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China.
  • 3. Institute of School Health, Yunnan Center for Disease Control and Prevention, 650032 Kunming, Yunnan, China.
  • 4. Department of Respiratory Medicine, the First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China.
  • 5. Department of General Medicine, the First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China.
  • 6. Department of Pathophysiology, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 637000 Nanchong, Sichuan, China.
  • 7. Scientific Research Laboratory Center, the First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China.
  • 8. Department of General Medicine, Kunming Yan'an Hospital, 650051 Kunming, Yunnan, China.
PMID: 38179732 DOI: 10.31083/j.fbl2812325
Abstract

Background: The mortality rate of colorectal Cancer (CRC) ranks second worldwide. Previous research had indicated that licochalcone A (LA) was a flavonoid in licorice with diverse Anticancer effects. We explored the underlying mechanisms of LA-triggered Anticancer activity in CRC.

Methods: Thiazolyl Blue (MTT) experiment and EdU staining were utilized to evaluate cell proliferation. Meanwhile, cells were stained by Annexin V/PI to investigate Apoptosis through flow cytometry assay. Moreover, expressions of proteins were detected by immunoblotting, and the level of related mRNA was investigated using real-time quantitative PCR.

Results: LA selectively suppressed the proliferation and triggered Apoptosis of CRC cells. Strikingly, LA induced cytoprotective autophagic activities since the suppression of Autophagy significantly strengthened LA-induced cytotoxicity and FLICE inhibitory protein (c-FLIPL) degradation, meanwhile reversing LA-mediated heat shock protein 70 (HSP70) upregulation. Moreover, autophagy-mediated HSP70 upregulation resisted LA-induced Anticancer effects since the suppression of HSP70 strengthened LA-triggered cytotoxicity and c-FLIPL degradation. Furthermore, LA greatly activated extracellular signal-regulated protein kinases (ERK) and p38. However, blocking of ERK, but not p38, significantly boosted LA-triggered cell death and c-FLIPL downregulation. Suppression of ERK also reversed LA-mediated autophagic induction.

Conclusions: LA increased HSP70 expression depending on ERK-mediated Autophagy, which protected CRC cells from LA-induced Anticancer activities.

Keywords
ERK; Hsp70; apoptosis; autophagy; colorectal cancer; licochalcone A.
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