Erianthridin Induces Non-small Cell Lung Cancer Cell Apoptosis through the Suppression of Extracellular Signal-regulated Kinase Activity

Sirima Boonjing; Sutthaorn Pothongsrisit; Onsurang Wattanathamsan; Boonchoo Sritularak; Varisa Pongrakhananon

doi:10.1055/a-1295-8606

Planta Medica, Table of Contents

Planta Med 2021; 87(04): 283-293
DOI: 10.1055/a-1295-8606

Biological and Pharmacological Activity

Original Papers

Erianthridin Induces Non-small Cell Lung Cancer Cell Apoptosis through the Suppression of Extracellular Signal-regulated Kinase Activity

Sirima Boonjing

¹Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

,

Sutthaorn Pothongsrisit

¹Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

,

Onsurang Wattanathamsan

²Inter-department Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand

,

Boonchoo Sritularak

³Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

,

Varisa Pongrakhananon

¹Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

⁴Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Research Cluster, Chulalongkorn University, Bangkok, Thailand

› Author Affiliations

Abstract

Due to the high mortality of lung cancer, natural derivative compounds have been promoted as versatile sources for anticancer drug discovery. Erianthridin, a phenanthrene compound isolated from Dendrobium formosum, exhibits intriguing apoptosis-inducing effects in non-small cell lung cancer cells. Apoptotic nuclei staining assays showed that apoptotic cells with DNA fragmentation and apoptotic bodies were apparent, and an increase in annexin V-FITC-positive cells were found in cells treated with erianthridin. The apoptosis protein markers for cleaved caspase-3 and cleaved poly-ADP-ribose polymerase were significantly upregulated in response to erianthridin. A mechanistic investigation revealed that erianthridin was able to attenuate extracellular signal-regulated kinase activity and thereby mediate apoptosis through the modulation of Bcl-2 family protein levels. U0126, an extracellular signal-regulated kinase inhibitor, augmented the apoptosis-inducing effect of erianthridin; in contrast, overexpression of exogenous extracellular signal-regulated kinase substantially abrogated erianthridin activity. Furthermore, an in vitro 3D tumorigenesis assay showed that erianthridin was able to potentially suppress lung cancer cell proliferation. This study is the first to report a promising cytotoxic effect of erianthridin, which provides preclinical evidence for further research and development of this compound.

Key words

apoptosis - Bcl-2 family proteins - Dendrobium densiflorum - erianthridin - extracellular signal-regulated kinase - Orchidaceae - non-small cell lung cancer cells

Full Text

References

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