Levofloxacin exerts broad-spectrum anticancer activity via regulation of THBS1, LAPTM5, SRD5A3, MFAP5 and P4HA1

Xiaoqiong He; Qian Yao; Duane D Hall; Zhongyu Song; Dan Fan; Yutong You; Wenjing Lian; Zhangping Zhou; Ling Duan; Biyi Chen

doi:10.1097/CAD.0000000000001194

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Levofloxacin exerts broad-spectrum anticancer activity via regulation of THBS1, LAPTM5, SRD5A3, MFAP5 and P4HA1

Journal article

Peer reviewed

Levofloxacin exerts broad-spectrum anticancer activity via regulation of THBS1, LAPTM5, SRD5A3, MFAP5 and P4HA1

Xiaoqiong He, Qian Yao, Duane D Hall, Zhongyu Song, Dan Fan, Yutong You, Wenjing Lian, Zhangping Zhou, Ling Duan and Biyi Chen

Anti-cancer drugs, Vol.33(1), pp.e235-e246

01/01/2022

DOI: 10.1097/CAD.0000000000001194

PMID: 34419964

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Abstract

One cost-effective way for identifying novel cancer therapeutics is in the repositioning of available drugs for which current therapies are inadequate. Levofloxacin prevents DNA duplication in bacteria by inhibiting the activity of DNA helicase. As eukaryotic cells have similar intracellular biologic characteristics as prokaryotic cells, we speculate that antibiotics inhibiting DNA duplication in bacteria may also affect the survival of cancer cells. Here we report that levofloxacin significantly inhibited the proliferation and clone formation of cancer cells and xenograft tumor growth through cell cycle arrest at G2/M and by enhancing apoptosis. Levofloxacin significantly altered gene expression in a direction favoring anticancer activity. THBS1 and LAPTM5 were dose-dependently upregulated whereas SRD5A3, MFAP5 and P4HA1 were downregulated. Pathway analysis revealed that levofloxacin significantly regulated canonical oncogenic pathways. Specific network enrichment included a MAPK/apoptosis/cytokine-cytokine receptor interaction pathway network that associates with cell growth, differentiation, cell death, angiogenesis and development and repair processes and a bladder cancer/P53 signaling pathway network mediating the inhibition of angiogenesis and metastasis. THBS1 overlapped in 16 of the 22 enriched apoptotic pathways and the 2 pathways in the bladder cancer/P53 signaling pathway network. P4HA1 enriched in 7 of the top 10 molecular functions regulated by differential downregulated genes. Our results indicate that levofloxacin has broad-spectrum anticancer activity with the potential to benefit cancer patients already treated or requiring prophylaxis for an infectious syndrome. The efficacy we find with levofloxacin may provide insight into the discovery and the design of novel less toxic anticancer drugs.

Animals

Apoptosis - drug effects

Cell Adhesion Molecules - drug effects

Cell Line, Tumor

Cell Proliferation - drug effects

Cytokines - drug effects

DNA Helicases - drug effects

Dose-Response Relationship, Drug

Gene Expression Regulation, Neoplastic - drug effects

Humans

Levofloxacin - pharmacology

Male

Membrane Proteins - drug effects

Mice

Mice, Inbred BALB C

Mice, Nude

Mitogen-Activated Protein Kinases - drug effects

Signal Transduction - drug effects

Xenograft Model Antitumor Assays

Details

Title: Subtitle: Levofloxacin exerts broad-spectrum anticancer activity via regulation of THBS1, LAPTM5, SRD5A3, MFAP5 and P4HA1
Creators: Xiaoqiong He - Kunming Medical University
Qian Yao - Kunming Medical University
Duane D Hall - Roy J. and Lucille A. Carver College of Medicine
Zhongyu Song - Kunming Medical University
Dan Fan - Kunming Medical University
Yutong You - Kunming Medical University
Wenjing Lian - Kunming Medical University
Zhangping Zhou - Kunming Medical University
Ling Duan - Kunming Medical University
Biyi Chen - University of Iowa
Resource Type: Journal article
Publication Details: Anti-cancer drugs, Vol.33(1), pp.e235-e246
DOI: 10.1097/CAD.0000000000001194
PMID: 34419964
ISSN: 1473-5741
eISSN: 1473-5741
Language: English
Date published: 01/01/2022
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984359594602771

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