Evidence map›Paper›PMID 40127816›Full record

ArticleCancer letters2025

Targeting mitochondrial ribosomal protein expression by andrographolide and melatonin for colon cancer treatment.

Advaitha Midde, Navpreet Arri, Tibor Kristian, Suprabhat Mukherjee, Parth Sarthi Sen Gupta, Yuji Zhang, Mariuz Karbowski, Jaylyn Waddell, Nagarajan Maharajan, Md Sazzad Hassan and 3 more

Erratum issuedAbstract read
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In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Advaitha MiddeDepartment of Pediatrics, University of Maryland School of Medicine (UMSOM), Baltimore, MD, USA.
Navpreet ArriDepartment of Pediatrics, University of Maryland School of Medicine (UMSOM), Baltimore, MD, USA.
Tibor KristianVAMHCS, UMSOM, Baltimore, MD, USA; Department of Anesthesiology and the Center for Shock, Trauma, and Anesthesiology Research (STAR), UMSOM, Baltimore, MD, USA.
Suprabhat MukherjeeIntegrative Biochemistry & Immunology Laboratory(IBIL), Department of Animal Science, Kazi Nazrul University, Asansol, India.
Parth Sarthi Sen GuptaSchool of Biosciences and Bioengineering, DY Patil International University, Pune, India.
Yuji ZhangDivision of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, UMSOM, Baltimore, MD, USA.
Mariuz KarbowskiDepartment of Biochemistry and Molecular Biology, UMSOM, Baltimore, MD, USA.
Jaylyn WaddellDepartment of Pediatrics, University of Maryland School of Medicine (UMSOM), Baltimore, MD, USA.
Nagarajan MaharajanDepartment of Biochemistry and Molecular Biology, UMSOM, Baltimore, MD, USA; Department of Otorhinolaryngology-Head & Neck Surgery, UMSOM, Baltimore, MD, USA.
Md Sazzad HassanDepartment of Surgery, Indiana University School of Medicine, South Bend, IN, USA; Harper Cancer Research Institute, South Bend, IN, USA.
Heather M O'HaganMedical Sciences Program, Indiana University School of Medicine, Bloomington, IN, USA; Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Michal ZalzmanDepartment of Biochemistry and Molecular Biology, UMSOM, Baltimore, MD, USA; Department of Otorhinolaryngology-Head & Neck Surgery, UMSOM, Baltimore, MD, USA.
Aditi BanerjeeDepartment of Pediatrics, University of Maryland School of Medicine (UMSOM), Baltimore, MD, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), USA. Electronic address: aditi.banerjee@som.umaryland.edu.

Funding

Cell Type Specific Transcriptional Cascades in Inner Ear DevelopmentR01DC013817 · NIDCD · UNIVERSITY OF MARYLAND BALTIMORE · PI HERTZANO, RONNA · 2015 to 2022
$3.6M
Targeting mitochondrial Complex I in neonatal hypoxia-ischemiaR01NS122777 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI BRIAN M POLSTER, JAYLYN Waddell WADDELL · 2022 to 2026
$2.5M
Using NAD+ precursor for treatment of global cerebral ischemiaR01NS119275 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KRISTIAN, TIBOR · 2021 to 2025
$1.9M
Cell Type Specific Transcriptional Cascades in Inner Ear DevelopmentU01DC013817 · NIDCD · UNIVERSITY OF MARYLAND BALTIMORE · PI AHMED, ZUBAIR M. · 2023 to 2025
$1.6M
BLRD VA I01 BX004895NIDCD NIH HHS R01 DC013817NIDCD NIH HHS U01 DC013817NINDS NIH HHS R01 NS119275NINDS NIH HHS R01 NS122777
6 · The paper itself

Abstract

Colospheroids contain colon cancer stem cells (CSCs) that cause colorectal cancer metastasis (mCRC). Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the U.S. Little is known about the role of mitochondria in the survival and metastatic ability of CSCs. In this study, we investigate the effect of andrographolide (AGP) and melatonin (MLT) on mitochondrial dynamics (including fusion and fission) and the expression of mitochondrial ribosomal proteins (MRPs). Our results show that AGP and MLT synergistically reduce the total active mitochondrial mass, downregulate fusion and fission proteins, reduce OXPHOS proteins, and lead to CSC growth inhibition via Nrf2 and KEAP1 signaling. Microarray revealed 4389 differentially expressed mRNAs in the AGP and MLT combination compared to the control. Results exhibiting a three-fold induction/reduction were validated by qRT-PCR and immunoblot. MRPS6, a mitochondrial ribosomal (Mitoribosome) small subunit protein, was dramatically downregulated by AGP + MLT treatment compared to control. MRPS6 inhibition by siRNA reduced mCRC cell viability. Molecular docking-based protein-ligand interactions showed that AGP has direct physical interaction with MRPS6 and increases the binding affinity of MLT to MRPS6. This drug combination downregulated genes in the NRF2 (NFE2L2) pathway in CSCs. MRPS6 may be directly linked to CSC proliferation and could be a therapeutic target for this population. Functionally, MRPS6 knockdown significantly reduced colony formation, with enhanced suppression in AGP + MLT-treated cells. In xenograft models, the AGP-MLT combination synergistically decreased MRPS6 expression and increased apoptosis, as evidenced by TUNEL assays, demonstrating the therapeutic potential of targeting MRPS6 in CRC.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsColonic NeoplasmsDiterpenesMelatoninMitochondrial ProteinsRibosomal ProteinsAnimalsCell Line, TumorCell ProliferationCell SurvivalGene Expression Regulation, NeoplasticHumansKelch-Like ECH-Associated Protein 1MiceMice, NudeMitochondriaandrographolideDiterpenesKEAP1 protein, humanKelch-Like ECH-Associated Protein 1MelatoninMitochondrial ProteinsNFE2L2 protein, humanNF-E2-Related Factor 2Ribosomal ProteinsAndrographolideColon cancer stem cellsColospheroids (3D spheroids culture model)Fusion-fission proteinMelatoninMitochondrial dynamicsMitochondrial massMitochondrial ribosomal protein

Identifiers

PMID40127816
PMCPMC12810355

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.