Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in
Wai M Liu1, Katherine A Scott1, Jayne L Dennis1
1Department of Oncology, Institute for Infection and Immunity, St. George's University of London, London SW17 0RE, UK.
Abstract:
It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49±7.0 vs. 14±2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32±1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule.
Insights
Low-dose naltrexone (LDN) shows anticancer activity by affecting cell signaling and immune responses. Modifying LDN treatment schedules enhances its efficacy and cancer cell killing potential.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Low-dose naltrexone (LDN) has demonstrated potential in reducing tumor growth.
- Its mechanisms involve interference with cancer cell signaling and immune system modulation.
Purpose of the Study:
- To investigate the gene expression profile of cancer cells treated with LDN.
- To assess the impact of altered LDN treatment schedules on anticancer efficacy.
- To evaluate LDN's potential to enhance chemotherapy effectiveness.
Main Methods:
- Gene expression profiling of a cancer cell line after LDN treatment.
- Comparative analysis of continuous vs. intermittent LDN treatment schedules.
- Assessment of LDN pre-treatment on cancer cell sensitivity to chemotherapy agents.
Main Results:
- LDN selectively modulated genes involved in cell cycle regulation and immune response.
- Pro-apoptotic genes BAD and BIK1 expression increased following LDN treatment.
- Intermittent LDN treatment schedules enhanced cancer cell killing compared to continuous treatment.
- LDN priming increased cancer cell sensitivity to chemotherapy agents like oxaliplatin.
Conclusions:
- LDN exhibits anticancer properties through effects on cell signaling and immunity.
- Optimizing LDN treatment schedules can significantly improve its anticancer efficacy.
- LDN can act as a sensitizer to conventional chemotherapy, offering a potential strategy for enhanced cancer treatment.
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