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Updated: May 29, 2026
A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
Published on: March 10, 2017
Bioluminescence-based high-throughput screen identifies pharmacological agents that target neurotransmitter signaling
Ma Reina D Improgo1, Christopher W Johnson, Andrew R Tapper
1Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Background:
Frontline treatment of small cell lung carcinoma (SCLC) relies heavily on chemotherapeutic agents and radiation therapy. Though SCLC patients respond well to initial cycles of chemotherapy, they eventually develop resistance. Identification of novel therapies against SCLC is therefore imperative.
Methods And Findings:
We have designed a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents. The assay was first validated via standard pharmacological agents and RNA interference using two human SCLC cell lines. We then utilized the assay in a high-throughput screen using the LOPAC(1280) compound library. The screening identified several drugs that target classic cancer signaling pathways as well as neuroendocrine markers in SCLC. In particular, perturbation of dopaminergic and serotonergic signaling inhibits SCLC cell viability.
Conclusions:
The convergence of our pharmacological data with key SCLC pathway components reiterates the importance of neurotransmitter signaling in SCLC etiology and points to possible leads for drug development.
Insights
Novel therapies are needed for small cell lung carcinoma (SCLC) due to treatment resistance. A new assay identified that targeting neurotransmitter signaling, specifically dopaminergic and serotonergic pathways, inhibits SCLC cell viability.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Frontline treatment for small cell lung carcinoma (SCLC) involves chemotherapy and radiation.
- SCLC patients often develop resistance to initial chemotherapy treatments.
- There is a critical need for novel therapeutic strategies against SCLC.
Purpose of the Study:
- To develop and validate a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents.
- To identify novel drug candidates targeting SCLC through a high-throughput screen.
Main Methods:
- Designed a bioluminescence-based cell viability assay.
- Validated the assay using standard pharmacological agents and RNA interference in human SCLC cell lines.
- Screened the LOPAC(1280) compound library using the developed assay.
Main Results:
- Identified several drugs targeting classic cancer signaling pathways and neuroendocrine markers in SCLC.
- Demonstrated that perturbation of dopaminergic and serotonergic signaling significantly inhibits SCLC cell viability.
- Validated the utility of the assay for identifying potential SCLC therapeutics.
Conclusions:
- Neurotransmitter signaling pathways are crucial in SCLC etiology.
- Targeting dopaminergic and serotonergic signaling presents a promising avenue for SCLC drug development.
- The developed assay is effective for identifying novel anti-SCLC agents.
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