# Kadukkai maathirai (Indian herbal drug) prevents hepatocellular cancer progression by enhancing GSTM1 expression and modulating β catenin transcription: in-silico and in-vivo study

**Authors:** Manjunath Shetty, Smita Shenoy, Arul Amuthan, Vasudha Devi, Nitesh Kumar, Amruth Kiran, Ganesh Shenoy, Diya Rajasekhar Chinta, Shama Prasada K, Akshatha Shetty, Mohandas Rao K G, Talha Bin Emran, Haiyang Yu

PMC · DOI: 10.12688/f1000research.145961.1 · F1000Research · 2024-06-17

## TL;DR

This study shows that Kadukkai maathirai, an Indian herbal drug, may help prevent liver cancer progression by boosting detox enzymes and affecting cancer-related proteins.

## Contribution

The study demonstrates the novel preventive effect of Kadukkai maathirai on HCC through GSTM1 upregulation and β catenin modulation.

## Key findings

- Kadukkai maathirai reduced nodule count and improved liver health in HCC-induced rats.
- The herbal drug increased GSTM1 expression, a key detox enzyme in liver cancer prevention.
- Phytoconstituents in Kadukkai maathirai inhibited the β catenin armadillo repeat region in silico.

## Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor clinical outcomes. Hence cost-effective drugs with fewer side effects as a standard supportive therapy might yield substantial advantages in efficacy and safety.
Kadukkai maathirai (KM) is being used as a supplement in hepatocellular carcinoma
. We evaluated whether KM has any preventive action on cancer progression in diethyl nitrosamine (DEN) - induced HCC in rats.

DEN was injected to produce HCC in rats, which was confirmed after 16 weeks. All the rats were orally administered KM for 4 weeks. Hepatoprotective potential (serum AST, ALT, ALP, Bilirubin) and anticancer efficacy (body weight, nodule count, tumor progression by histopathology, expression of GSTM1 by Liquid chromatography-mass spectrometry (LC-MS), and In-silico analysis of phytoconstituents against β catenin and LRP analysis were evaluated.

KM prevented cancer progression against DEN-induced HCC by an increase in GSTM1, a phase II detoxifying enzyme. It significantly reversed altered nodule count, relative liver weight, body weight, and histopathological features of HCC.
In silico analysis of phytoconstituents of KM showed that they modulate the intracellular transcription process by inhibiting the armadillo repeat region of β catenin.

Our results elucidate the potential of KM as a supplement in HCC by reducing nodule count, protecting the liver from further damage, GSTM1 expression, and inhibiting armadillo repeat region of β catenin.

## Linked entities

- **Genes:** GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944], ctnnb1.S (catenin beta 1 S homeolog) [NCBI Gene 380441]
- **Proteins:** ctnnb1.S (catenin beta 1 S homeolog)
- **Chemicals:** diethyl nitrosamine (PubChem CID 5921), ALT (PubChem CID 10219674), ALP (PubChem CID 1392), Bilirubin (PubChem CID 5280352)
- **Diseases:** Hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** LRP1 (LDL receptor related protein 1) [NCBI Gene 4035] {aka A2MR, APOER, APR, CD91, DDH3, IGFBP-3R}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, ATHS (atherosclerosis susceptibility (lipoprotein associated)) [NCBI Gene 470] {aka ALP}, GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944] {aka GST1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4, GTM1}
- **Diseases:** cancer (MESH:D009369), HCC (MESH:D006528)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

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## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC11800331/full.md

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Source: https://tomesphere.com/paper/PMC11800331