# Electrolyzed Hydrogen Water Improves Chemosensitivity to Anticancer Drugs by Potently Suppressing Autophagy

**Authors:** Satoshi Yano, Liangjing Xie, Jinjuan Li, Yuka Sugaya, Yuki Miyauchi, Shigeru Kabayama, Taichi Hara

PMC · DOI: 10.1111/jcmm.71011 · Journal of Cellular and Molecular Medicine · 2026-02-17

## TL;DR

Electrolyzed hydrogen water helps cancer drugs work better by reducing a cell survival process called autophagy.

## Contribution

EHW is shown to suppress autophagy and enhance chemosensitivity through mTORC1 activation.

## Key findings

- EHW suppresses autophagy by activating mTORC1 signaling.
- Combining EHW with anticancer drugs reduces cancer cell viability.
- EHW may be a safe adjuvant for cancer therapy due to its autophagy-inhibiting effects.

## Abstract

Autophagy is an intracellular recycling system that contributes to the maintenance of cellular homeostasis. However, by providing tolerance to various stressors, autophagy promotes the survival and proliferation of cancer cells and confers resistance to chemotherapy. Anticancer drugs activate autophagy, leading to drug resistance in cancer cells. Autophagy inhibitors, such as chloroquine and hydroxychloroquine, enhance the antitumor effects of anticancer drugs when used in combination with them. However, these inhibitors are associated with several adverse effects. Here, using genome‐wide RNA sequencing analysis, we deciphered a novel function of electrolyzed hydrogen water (EHW) in suppressing autophagy by activating mammalian target of rapamycin complex 1 signalling. The combination of EHW with anticancer drugs, such as 5‐fluorouracil or paclitaxel, which activate autophagy, significantly decreased the viability of cervical and colorectal cancer cells. Mechanistically, molecular hydrogen and trace elements in EHW may suppress autophagy and potentiate anticancer effects. Considering its safety, we propose that EHW can act as a novel adjuvant to anticancer therapy.

## Linked entities

- **Proteins:** Crtc (CREB-regulated transcription coactivator)
- **Chemicals:** 5-fluorouracil (PubChem CID 3385), paclitaxel (PubChem CID 36314), chloroquine (PubChem CID 2719), hydroxychloroquine (PubChem CID 3652)
- **Diseases:** cervical cancer (MONDO:0002974), colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** CHAC1 (ChaC glutathione specific gamma-glutamylcyclotransferase 1) [NCBI Gene 79094], TMEM158 (transmembrane protein 158) [NCBI Gene 25907] {aka BBP, RIS1, p40BBP}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, SESN2 (sestrin 2) [NCBI Gene 83667] {aka HI95, SES2, SEST2}, STC1 (stanniocalcin 1) [NCBI Gene 6781] {aka STC}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, RPS6KB1 (ribosomal protein S6 kinase B1) [NCBI Gene 6198] {aka PS6K, S6K, S6K-beta-1, S6K1, STK14A, p70 S6KA}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, IL11 (interleukin 11) [NCBI Gene 3589] {aka AGIF, IL-11}, ATG9A (autophagy related 9A) [NCBI Gene 79065] {aka APG9L1, MGD3208, mATG9}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Atg7 (autophagy related 7) [NCBI Gene 74244] {aka 1810013K23Rik, Agp7, Apg7l, Atg7l, Gm21553}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, LIF (LIF interleukin 6 family cytokine) [NCBI Gene 3976] {aka CDF, DIA, HILDA, MLPLI}, Rps6kb1 (ribosomal protein S6 kinase B1) [NCBI Gene 72508] {aka 2610318I15Rik, P70S6K1, S6K, S6K-beta-1, S6K1, p70 S6K-alpha}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Atg5 (autophagy related 5) [NCBI Gene 11793] {aka 2010107M05Rik, 3110067M24Rik, Apg5l, Atg5l, Paddy}, DDIT4 (DNA damage inducible transcript 4) [NCBI Gene 54541] {aka Dig2, REDD-1, REDD1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** benign liver tumours (MESH:D008113), allergies (MESH:D004342), gastric damage (MESH:D013272), renal dysfunction (MESH:D007674), inflammatory bowel disease (MESH:D015212), cytotoxic (MESH:D064420), insulin resistance (MESH:D007333), cervical and colorectal cancer (MESH:D015179), cervical (MESH:D002575), acute kidney injury (MESH:D058186), toxic retinopathy (MESH:D058437), EHW (MESH:D000069578), cancer (MESH:D009369), cervical cancer (MESH:D002583), inflammatory (MESH:D007249), injury (MESH:D014947)
- **Chemicals:** CQ (MESH:D002738), ROS (MESH:D017382), Tween 20 (MESH:D011136), Hydrogen (MESH:D006859), alcohol (MESH:D000438), polyvinylidene difluoride (MESH:C024865), paraformaldehyde (MESH:C003043), polybrene (MESH:D006583), hydroxide (MESH:C031356), Bicinchoninic Acid (MESH:C047117), CO2 (MESH:D002245), HCQ (MESH:D006886), 3-MA (MESH:C025946), puromycin (MESH:D011691), penicillin (MESH:D010406), charcoal (MESH:D002606), D-MEM (-), HCl (MESH:D006851), bafilomycin A1 (MESH:C040929), SDS (MESH:D012967), vanadium (MESH:D014639), TB (MESH:D013725), TRIzol (MESH:C411644), WATER (MESH:D014867), 5-FU (MESH:D005472), Triton X-100 (MESH:D017830), carbon (MESH:D002244), streptomycin (MESH:D013307), Baf. (MESH:C012071), ethylenediaminetetraacetic acid (MESH:D004492), Paclitaxel (MESH:D017239), formazan (MESH:D005562), platinum (MESH:D010984), NaCl (MESH:D012965)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** T2A
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HeLa cervical cancer — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_JX14), -8 — Xenopus laevis (African clawed frog), Spontaneously immortalized cell line (CVCL_4564), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), OUMS-36 T-1 — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_3092), HEK293FT — Homo sapiens (Human), Transformed cell line (CVCL_6911), MEFs — Mus musculus (Mouse), Finite cell line (CVCL_9115)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12912942/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12912942/full.md

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Source: https://tomesphere.com/paper/PMC12912942