Formosanin C suppresses cancer cell proliferation and migration by impeding autophagy machinery.

Abstract

Formosanin C (FC) is a natural compound extracted from Paris formosana Hayata with anticancer activity. FC induces both autophagy and apoptosis in human lung cancer cells. FC-induced depolarization of mitochondrial membrane potential (MMP) may trigger mitophagy. In this study, we clarified the effect of FC on autophagy, mitophagy, and the role of autophagy in FC-related cell death and motility. We found FC caused the continuous increase of LC3 II (representing autophagosomes) from 24 to 72 h without degradation after treatment of lung and colon cancer cells, indicating that FC blocks autophagic progression. In addition, we confirmed that FC also induces early stage autophagic activity. Altogether, FC is not only an inducer but also a blocker of autophagy progression. Moreover, FC increased MMP accompanied by overexpression of COX IV (mitochondria marker) and phosphorylated Parkin (p-Parkin, mitophagy marker) in lung cancer cells, but no colocalization of LC3 with COX IV or p-Parkin was detected under confocal microscopy. Moreover, FC could not block CCCP (mitophagy inducer)-induced mitophagy. These results imply that FC disrupts mitochondria dynamics in the treated cells, and the underlying mechanism deserves further exploration. Functional analysis reveals that FC suppresses cell proliferation and motility through apoptosis and EMT-related pathway, respectively. In conclusion, FC acts as an inducer as well as a blocker of autophagy that results in cancer cell apoptosis and decreased motility. Our findings shed the light on the development of combined therapy with FC and clinical anticancer drugs for cancer treatment.

• Authors: Man-Ling Chu, Pei-Wen Lin, Yu-Wen Liu, Shan-Ying Wu, Sheng-Hui Lan, Chun-Li Su, Hsiao-Sheng Liu
• Journal: The Kaohsiung journal of medical sciences (Kaohsiung J Med Sci) Vol. 39 Issue 5 Pg. 489-500 (May 2023) ISSN: 2410-8650 [Electronic] China (Republic : 1949- )
• PMID: 36866653 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.

Chemical References

• formosanin C
• Ubiquitin-Protein Ligases

Topics

• Humans
• Autophagy
• Ubiquitin-Protein Ligases (metabolism)
• Lung Neoplasms (drug therapy, genetics)
• Cell Proliferation