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

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

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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