Anticancer Activity of Fascaplysin against Lung Cancer Cell and Small Cell Lung Cancer Circulating Tumor Cell Lines

• Published in: Marine drugs Vol. 16; no. 10; p. 383
• Main Authors: Rath, Barbara, Hochmair, Maximilian, Plangger, Adelina, Hamilton, Gerhard
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.10.2018; MDPI
• Subjects: A549 Cells; Additives; Angiogenesis; Anticancer properties; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Biotechnology; Breast cancer; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Cell cycle; Cell Line, Tumor; Cell lines; Cells; Chemoresistance; Chemotherapy; circulating tumor cells; Cisplatin; Cisplatin - pharmacology; Colorectal cancer; Cyclin-dependent kinase 4; Cyclin-dependent kinases; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; Drugs; fascaplysin; Humans; Immunotherapy; Indoles; Indoles - pharmacology; Kinases; Lines; Lung cancer; Lung Neoplasms - drug therapy; Lungs; Marine invertebrates; Medical prognosis; Neoplasms; Neoplastic Cells, Circulating - drug effects; Non-small cell lung carcinoma; Ovarian cancer; Phosphorylation; Proteins; Signal transduction; Signal Transduction - drug effects; Small cell lung carcinoma; Spheroids; Tumor cell lines; Tumors; Vascular endothelial growth factor; lung cancer; fascaplysin; circulating tumor cells; cisplatin; signal transduction; cytotoxicity
• DOI: 10.3390/md16100383
• ISSN: 1660-3397

Lung cancer is a leading cause of tumor-associated mortality. Fascaplysin, a bis-indole of a marine sponge, exhibit broad anticancer activity as specific CDK4 inhibitor among several other mechanisms, and is investigated as a drug to overcome chemoresistance after the failure of targeted agents or immunotherapy. The cytotoxic activity of fascaplysin was studied using lung cancer cell lines, primary Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) cells, as well as SCLC circulating tumor cell lines (CTCs). This compound exhibited high activity against SCLC cell lines (mean IC 0.89 µM), as well as SCLC CTCs as single cells and in the form of tumorospheres (mean IC 0.57 µM). NSCLC lines showed a mean IC of 1.15 µM for fascaplysin. Analysis of signal transduction mediators point to an ATM-triggered signaling cascade provoked by drug-induced DNA damage. Fascaplysin reveals at least an additive cytotoxic effect with cisplatin, which is the mainstay of lung cancer chemotherapy. In conclusion, fascaplysin shows high activity against lung cancer cell lines and spheroids of SCLC CTCs which are linked to the dismal prognosis of this tumor type. Derivatives of fascaplysin may constitute valuable new agents for the treatment of lung cancer.