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Regulatory role of Echinochrome A in cancer-associated fibroblast-mediated lung cancer cell migration

  • Da‑Young Eum (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Chaeyoung Lee (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Cong So Tran (College of Pharmacy and Research Institute for Drug Development, Pusan National University) ;
  • Jinyoung Lee (College of Pharmacy and Research Institute for Drug Development, Pusan National University) ;
  • Soon Yong Park (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Mi‑So Jeong (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Yunho Jin (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Jae Woong Shim (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Seoung Rak Lee (College of Pharmacy and Research Institute for Drug Development, Pusan National University) ;
  • Minseob Koh (Department of Chemistry, Pusan National University) ;
  • Elena A. Vasileva (G.B. Elyakov Pacifc Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science) ;
  • Natalia P. Mishchenko (G.B. Elyakov Pacifc Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science) ;
  • Seong‑Joon Park (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Si Ho Choi (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Yoo Jin Choi (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Hwayoung Yun (College of Pharmacy and Research Institute for Drug Development, Pusan National University) ;
  • Kyu Heo (Research Center, Dongnam Institute of Radiological & Medical Sciences)
  • 투고 : 2024.01.08
  • 심사 : 2024.03.13
  • 발행 : 2024.07.15

초록

Echinochrome A (Ech A), a marine biosubstance isolated from sea urchins, is a strong antioxidant, and its clinical form, histochrome, is being used to treat several diseases, such as ophthalmic, cardiovascular, and metabolic diseases. Cancer-associated fibroblasts (CAFs) are a component of the tumor stroma and induce phenotypes related to tumor malignancy, including epithelial-mesenchymal transition (EMT) and cancer stemness, through reciprocal interactions with cancer cells. Here, we investigated whether Ech A modulates the properties of CAFs and alleviates CAF-induced lung cancer cell migration. First, we observed that the expression levels of CAF markers, Vimentin and fibroblast-activating protein (FAP), were decreased in Ech A-treated CAF-like MRC5 cells. The mRNA transcriptome analysis revealed that in MRC5 cells, the expression of genes associated with cell migration was largely modulated after Ech A treatment. In particular, the expression and secretion of cytokine and chemokine, such as IL6 and CCL2, stimulating cancer cell metastasis was reduced through the inactivation of STAT3 and Akt in MRC5 cells treated with Ech A compared to untreated MRC5 cells. Moreover, while conditioned medium from MRC5 cells enhanced the migration of non-small cell lung cancer cells, conditioned medium from MRC5 cells treated with Ech A suppressed cancer cell migration. In conclusion, we suggest that Ech A might be a potent adjuvant that increases the efficacy of cancer treatments to mitigate lung cancer progression.

키워드

과제정보

This work was supported by the a Dongnam Institute of Radiological & Medical Sciences (DIRAMS) grant funded by the Korean government (MSIT) (50591-2023), a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2021R1A2C1095736) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2023R1A2C1007018).

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