Rosthorin A inhibits non-small cell lung cancer cell growth and metastasis through repressing epithelial-mesenchymal transition via downregulating Slug.

Abstract

Lung cancer always ranks first in the number of cancer deaths every year, accounting for 18.4% of total cancer deaths in 2018. Metastasis is the main cause of death in lung cancer patients. The identification of bioactive components of traditional Chinese medicine is very important for the development of novel reagents against non-small cell lung cancer (NSCLC). Rosthorin A has originated from Rabdosia rosthornii (Diels) Hara which excerpts from 'Chinese materia medica', and is known to have 'clear heat phlegm' properties in the folk. Little is known about the biological functions and mechanisms of Rosthorin A in cancer cells at present. The role of EMT in metastasis of a tumor cell is self-evident. Slug is an important EMT inducer, which is related to the development of lung cancer. Cell growth, clone assay, cell migration, cell invasion, and protein expression, and NSCLC transplanted tumor growth were performed in A549, H1299, and H1975 cells. Rosthorin A significantly inhibited the growth of NSCLC cells, it could prolong the survival of nude mice. Rosthorin A inhibited the migration and invasion of A549, H1299, and H1975 cells. Rosthorin A up-regulated E-cadherin expression level and down-regulated the expression of β-catenin, N-cadherin, vimentin, Slug, and Twist. Rosthorin A could promote the expression of E-cadherin and inhibit the development of EMT by downregulating Slug, to inhibit the development and metastasis of NSCLC cells. In summary, Rosthorin A could be used as a promising candidate for the treatment of NSCLC patients with recurrence and metastasis.

• Authors: Lulu Ni, Zhongjie Li, Xuelin Shi, Chao Yao, Jiangnan Sun, Min Ai, Shuangshuang Li, Yixiao Liu, Fei Xu, Yuetao Zhou, Jiangan Li, Liying Qiu
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 31 Issue 10 Pg. 997-1003 (11 2020) ISSN: 1473-5741 [Electronic] England
• PMID: 33065690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CTNNB1 protein, human
• Drugs, Chinese Herbal
• Nuclear Proteins
• Polyphenols
• SNAI1 protein, human
• Snail Family Transcription Factors
• TWIST1 protein, human
• Twist-Related Protein 1
• VIM protein, human
• Vimentin
• beta Catenin
• rosthorin A

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Mice, Inbred BALB C
• Nuclear Proteins (metabolism)
• Polyphenols (chemistry, pharmacology)
• Snail Family Transcription Factors (metabolism)
• Twist-Related Protein 1 (metabolism)
• Vimentin (metabolism)
• Xenograft Model Antitumor Assays
• beta Catenin (metabolism)