---
title: "Lonidamine plus devimistat produces synergistic antitumor effects in NSCLC by disrupting cellular"
id: "pubmed-42627059"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42627059"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42627059/"
doi: "10.3892/or.2026.9184"
published_at: "2026-08-21T12:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Lonidamine plus devimistat produces synergistic antitumor effects in NSCLC by disrupting cellular
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42627059
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42627059/)
- **DOI:** [10.3892/or.2026.9184](https://doi.org/10.3892%2For.2026.9184)
- **Published At:** 2026-08-21T12:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Disrupting tumor **energy metabolism** is a promising strategy for non‑small cell lung cancer (NSCLC), but single‑pathway approaches have been inadequate because cancer cells adapt via multiple metabolic routes. - The study tested a combination of the metabolic inhibitors **lonidamine** and **devimistat** in A549 NSCLC models to target **glycolysis**, the **tricarboxylic acid (TCA) cycle**, and **oxidative phosphorylation** simultaneously. - Efficacy was evaluated both _in vitro_ and _in vivo_, including assays for cytotoxicity, colony formation, optimal combination dosing, mitochondrial function, ATP levels, reactive oxygen species (ROS), and apoptosis, plus pharmacodynamic measurements in a xenograft mouse model. - Characteristic metabolite levels were measured to assess impacts on cellular energy metabolism pathways. - Combination therapy produced synergistic inhibition of tumor growth in cell culture and in xenograft mice, compared with single agents. - Mechanistically, the combined treatment induced **ROS** production, reduced **ATP** generation, and impaired mitochondrial morphology and function, culminating in activation of apoptosis in tumor cells via metabolic regulation. - The findings support the rationale that simultaneously targeting multiple aspects of tumor energy metabolism can enhance antitumor effects in lung cancer. - Specific quantitative results, detailed dosing regimens, statistical measures, and full experimental protocols were not reported in the abstract and would require consultation of the full text for complete data.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 21. # Combination of lonidamine with devimistat induces synergistic antitumor effects in lung cancer via multifaceted disruption of cellular energy metabolism [Xinhe Bai](https://pubmed.ncbi.nlm.nih.gov/?term=Bai+X&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yongfeng Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yuling Luo](https://pubmed.ncbi.nlm.nih.gov/?term=Luo+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Pei Jing](https://pubmed.ncbi.nlm.nih.gov/?term=Jing+P&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Xia Hong](https://pubmed.ncbi.nlm.nih.gov/?term=Hong+X&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yaqin Zou](https://pubmed.ncbi.nlm.nih.gov/?term=Zou+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yan Dai](https://pubmed.ncbi.nlm.nih.gov/?term=Dai+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Xuping Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+X&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Meiling Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+M&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Han Xiao](https://pubmed.ncbi.nlm.nih.gov/?term=Xiao+H&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yilan Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Shiwei Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+S&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Qingze Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+Q&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#full-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.") Affiliations Expand ### Affiliation * 1 Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. * PMID: **42627059** * DOI: [ 10.3892/or.2026.9184 ](https://doi.org/10.3892/or.2026.9184) Item in Clipboard # Combination of lonidamine with devimistat induces synergistic antitumor effects in lung cancer via multifaceted disruption of cellular energy metabolism Xinhe Bai et al. Oncol Rep. 2026 Oct. Show details Display options Display options Format Abstract PubMed PMID Oncol Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Oncol+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Oncol+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42627059/) . 2026 Oct;56(4):178. doi: 10.3892/or.2026.9184. Epub 2026 Aug 21. ### Authors [Xinhe Bai](https://pubmed.ncbi.nlm.nih.gov/?term=Bai+X&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yongfeng Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yuling Luo](https://pubmed.ncbi.nlm.nih.gov/?term=Luo+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Pei Jing](https://pubmed.ncbi.nlm.nih.gov/?term=Jing+P&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Xia Hong](https://pubmed.ncbi.nlm.nih.gov/?term=Hong+X&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yaqin Zou](https://pubmed.ncbi.nlm.nih.gov/?term=Zou+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yan Dai](https://pubmed.ncbi.nlm.nih.gov/?term=Dai+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Xuping Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+X&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Meiling Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+M&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Han Xiao](https://pubmed.ncbi.nlm.nih.gov/?term=Xiao+H&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Yilan Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+Y&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Shiwei Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+S&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."), [Qingze Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+Q&cauthor_id=42627059)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42627059/#short-view-affiliation-1 "Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.") ### Affiliation * 1 Department of Pharmacy, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China. * PMID: **42627059** * DOI: [ 10.3892/or.2026.9184 ](https://doi.org/10.3892/or.2026.9184) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Disrupting energy metabolic pathways has emerged as a promising strategy for cancer therapy including non‑small cell lung cancer (NSCLC). However, the ultimate anticancer effects have not been satisfactory. This is likely because cellular energy metabolism encompasses multiple processes and pathways, and tumor cells can flexibly regulate these processes and pathways to adapt to external disturbances and changes in the microenvironment in order to maintain their growth and proliferation. As a result, current strategies which only target certain aspects of energy metabolism have not achieved commendable results. In the present study, two inhibitors lonidamine and devimistat, each with their own limitations, were combined to treat A549 NSCLC by synergistically interfering with the main aspects of cellular energy metabolism including glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. The synergistic potency was examined _in vitro_ and _in vivo_ including cytotoxicity, optimal combination doses, colony formation, mitochondrial function, adenosine triphosphate (ATP) and reactive oxygen species (ROS) production, apoptosis and pharmacodynamics in a xenograft mouse model. Moreover, characteristic metabolite levels were measured to elucidate the effects of combination treatment on cellular energy metabolism. The results showed that this combination therapy could synergistically inhibit tumor growth _in vitro_ and _in vivo_. Furthermore, combining these two metabolic inhibitors could induce the production of ROS, reduce the generation of ATP, impair mitochondrial morphology and function, and ultimately activate apoptosis in tumor cells through metabolic regulation, facilitating antitumor treatment. The findings underscore the necessity and effectiveness of targeting tumor energy metabolism for lung cancer therapy, providing reliable evidence that metabolic therapies can effectively participate in cancer treatment. **Keywords:** combination therapy; devimistat; glycolysis; lonidamine; non‑small cell lung cancer; oxidative phosphorylation; tricarboxylic acid cycle. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/38873997/) Wu S, Zhao Q, Liu S, Kuang J, Zhang J, Onga A, Shen Y, Wang J, Sui H, Ni L, Ye Y, Tu X, Le HB, Zheng Y, Cui R, Zhu W.Wu S, et al.Int J Oncol. 2024 Aug;65(2):77. doi: 10.3892/ijo.2024.5665. Epub 2024 Jun 14.Int J Oncol. 2024.PMID: 38873997Free PMC article. * [ Enhanced antitumor activity of 3-bromopyruvate in combination with rapamycin in vivo and in vitro. ](https://pubmed.ncbi.nlm.nih.gov/25644152/) Zhang Q, Pan J, Lubet RA, Komas SM, Kalyanaraman B, Wang Y, You M.Zhang Q, et al.Cancer Prev Res (Phila). 2015 Apr;8(4):318-26. doi: 10.1158/1940-6207.CAPR-14-0142. Epub 2015 Feb 2.Cancer Prev Res (Phila). 2015.PMID: 25644152Free PMC article. * [ Increasing cisplatin exposure promotes small-cell lung cancer transformation after a shift from glucose metabolism to fatty acid metabolism. ](https://pubmed.ncbi.nlm.nih.gov/40155472/) Zhao QY, Liu WJ, Wang JG, Li H, Lv JL, Wang Y, Wang C.Zhao QY, et al.J Cancer Res Clin Oncol. 2025 Mar 28;151(3):126. doi: 10.1007/s00432-025-06164-3.J Cancer Res Clin Oncol. 2025.PMID: 40155472Free PMC article. * [ Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non-small cell lung cancer cells via endoplasmic reticulum stress-mediated degradation of Mcl-1. ](https://pubmed.ncbi.nlm.nih.gov/32189414/) Zhang Q, Chen M, Cao L, Ren Y, Guo X, Wu X, Xu K.Zhang Q, et al.Mol Carcinog. 2020 Jun;59(6):590-603. doi: 10.1002/mc.23184. Epub 2020 Mar 18.Mol Carcinog. 2020.PMID: 32189414 * [ Advances in metformin‑based metabolic therapy for non‑small cell lung cancer (Review). ](https://pubmed.ncbi.nlm.nih.gov/35039878/) Chen N, Zhou YS, Wang LC, Huang JB.Chen N, et al.Oncol Rep. 2022 Mar;47(3):55. doi: 10.3892/or.2022.8266. Epub 2022 Jan 18.Oncol Rep. 2022.PMID: 35039878Free PMC article.Review. 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