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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Licochalcone A Inhibits Melanoma Cell Survival by Suppressing HSP75 (TRAP1) and Disrupting Cellular Redox and Energy Homeostasis

  • Yoon-Jin Lee1,2
  • Min Hyuk Choi3
  • Ki Dam Kim3
  • Sukh Que Park4
  • Youin Bae3
  • Yu Sung Choi3
  • Sang Han Lee1,2
  • Hae-Seon Nam1,5
  • Moon Kyun Cho1,3
5 affiliations
  1. 1Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31151, Republic of Korea
  2. 2Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea
  3. 3Department of Dermatology, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea
  4. 4Department of Neurosurgery, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea
  5. 5Department of Tropical Medicine, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea
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Abstract

Heat shock protein 75(HSP75), a mitochondrial chaperone of the HSP90 family, sustains tumor cell survival by restraining oxidative phosphorylation, favoring aerobic glycolysis, and limiting mitochondrial ROS to preserve redox homeostasis. Although Licochalcone A (LCA), a flavonoid isolated from licorice root, displays anticancer activity across diverse tumors, whether HSP75 suppression contributes to its anti-melanoma effects remains undefined. This study assessed HSP75 expression in melanoma and evaluated the anti-melanoma efficacy of LCA. Expression of HSP75 was compared between melanoma and normal skin specimens by Western blotting. G361 melanoma cells were exposed to LCA, after which HSP75 expression, cell viability (MTT and trypan blue assays), intracellular ROS, the GSH/GSSG balance, ATP-associated luminescence, AMPK phosphorylation, MMP2, and apoptosis-related proteins were examined. HSP75 was also silenced by siRNA in normal melanocytes (HEMn-MP) and G361 cells, alone or combined with LCA treatment, with HSP75, p-AMPK, MMP2, cleaved PARP, and cleaved caspase-3 assessed by Western blotting. Melanoma tissue showed elevated HSP75 relative to normal tissue. LCA reduced HSP75 expression and viability while raising ROS, shifting the GSH/GSSG ratio toward oxidative stress, and reducing ATP-associated luminescence. AMPK phosphorylation rose, MMP2 declined, and pro-apoptotic markers (Bax, cleaved caspase-3, cleaved PARP) increased. HSP75 knockdown alone reproduced the LCA-induced changes in ATP-associated luminescence, p-AMPK, cleaved PARP, cleaved caspase-3, and MMP2, and combined knockdown with LCA further enhanced these changes in G361 cells, which were largely attenuated in normal HEMn-MP melanocytes. LCA suppresses melanoma cell survival by inducing cellular oxidative stress, reducing ATP-associated luminescence, and promoting apoptosis, with HSP75 suppression contributing to the ATP/AMPK and apoptotic responses. These findings support further evaluation of LCA and HSP75 in melanoma.

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Cite

BibTeXRIS
BibTeX
@article{lee2026licochalcone,
  title = {{Licochalcone A Inhibits Melanoma Cell Survival by Suppressing HSP75 (TRAP1) and Disrupting Cellular Redox and Energy Homeostasis}},
  author = {Yoon-Jin Lee and Min Hyuk Choi and Ki Dam Kim and Sukh Que Park and Youin Bae and Yu Sung Choi and Sang Han Lee and Hae-Seon Nam and Moon Kyun Cho},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209103},
  url = {https://www.mdpi.com/1422-0067/27/20/9103},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Licochalcone A Inhibits Melanoma Cell Survival by Suppressing HSP75 (TRAP1) and Disrupting Cellular Redox and Energy Homeostasis
AU  - Yoon-Jin Lee
AU  - Min Hyuk Choi
AU  - Ki Dam Kim
AU  - Sukh Que Park
AU  - Youin Bae
AU  - Yu Sung Choi
AU  - Sang Han Lee
AU  - Hae-Seon Nam
AU  - Moon Kyun Cho
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209103
UR  - https://www.mdpi.com/1422-0067/27/20/9103
AB  - Heat shock protein 75(HSP75), a mitochondrial chaperone of the HSP90 family, sustains tumor cell survival by restraining oxidative phosphorylation, favoring aerobic glycolysis, and limiting mitochondrial ROS to preserve redox homeostasis. Although Licochalcone A (LCA), a flavonoid isolated from licorice root, displays anticancer activity across diverse tumors, whether HSP75 suppression contributes to its anti-melanoma effects remains undefined. This study assessed HSP75 expression in melanoma and evaluated the anti-melanoma efficacy of LCA. Expression of HSP75 was compared between melanoma and normal skin specimens by Western blotting. G361 melanoma cells were exposed to LCA, after which HSP75 expression, cell viability (MTT and trypan blue assays), intracellular ROS, the GSH/GSSG balance, ATP-associated luminescence, AMPK phosphorylation, MMP2, and apoptosis-related proteins were examined. HSP75 was also silenced by siRNA in normal melanocytes (HEMn-MP) and G361 cells, alone or combined with LCA treatment, with HSP75, p-AMPK, MMP2, cleaved PARP, and cleaved caspase-3 assessed by Western blotting. Melanoma tissue showed elevated HSP75 relative to normal tissue. LCA reduced HSP75 expression and viability while raising ROS, shifting the GSH/GSSG ratio toward oxidative stress, and reducing ATP-associated luminescence. AMPK phosphorylation rose, MMP2 declined, and pro-apoptotic markers (Bax, cleaved caspase-3, cleaved PARP) increased. HSP75 knockdown alone reproduced the LCA-induced changes in ATP-associated luminescence, p-AMPK, cleaved PARP, cleaved caspase-3, and MMP2, and combined knockdown with LCA further enhanced these changes in G361 cells, which were largely attenuated in normal HEMn-MP melanocytes. LCA suppresses melanoma cell survival by inducing cellular oxidative stress, reducing ATP-associated luminescence, and promoting apoptosis, with HSP75 suppression contributing to the ATP/AMPK and apoptotic responses. These findings support further evaluation of LCA and HSP75 in melanoma.
SN  - 1422-0067
ER  -