Formosanin C suppresses cancer cell proliferation and migration by impeding autophagy machinery
Man-Ling Chu1, Pei-Wen Lin1, Yu-Wen Liu1
1M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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.
Insights
Formosanin C (FC) is a natural compound that both induces and blocks autophagy, leading to cancer cell apoptosis and reduced motility. This dual action highlights FC
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Formosanin C (FC), a natural compound from Paris formosana Hayata, exhibits anticancer properties.
- FC is known to induce autophagy and apoptosis in human lung cancer cells.
- FC-induced mitochondrial membrane potential (MMP) depolarization suggests potential mitophagy involvement.
Purpose of the Study:
- To elucidate the effects of FC on autophagy and mitophagy.
- To investigate the role of autophagy in FC-mediated cancer cell death and motility.
- To clarify the dual role of FC in autophagic progression.
Main Methods:
- Treatment of lung and colon cancer cells with FC.
- Analysis of autophagosome markers (LC3 II) and autophagic flux.
- Assessment of mitochondrial membrane potential (MMP) and mitophagy markers (COX IV, p-Parkin).
- Confocal microscopy to detect colocalization of LC3 with mitochondrial markers.
- Evaluation of cell proliferation, motility, apoptosis, and EMT pathways.
Main Results:
- FC treatment led to a continuous increase in LC3 II without degradation, indicating blocked autophagic progression, while also inducing early-stage autophagy.
- FC increased MMP and upregulated COX IV and p-Parkin, but no LC3 colocalization with these markers was observed, suggesting disrupted mitochondria dynamics rather than direct mitophagy induction.
- FC suppressed cell proliferation and motility via apoptosis and EMT pathways, respectively.
Conclusions:
- FC acts as both an inducer and a blocker of autophagy, contributing to cancer cell apoptosis and reduced motility.
- FC disrupts mitochondria dynamics, a mechanism requiring further investigation.
- FC shows potential for combined therapeutic strategies with existing anticancer drugs.
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