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- Title
Cryptotanshinone inhibits PFK-mediated aerobic glycolysis by activating AMPK pathway leading to blockade of cutaneous melanoma.
- Authors
Chen, Qiong; Liu, Yang; Zhu, Yunxuan; Zhu, Ziyan; Zou, Jueyao; Pan, Yanhong; Lu, Yin; Chen, Wenxing
- Abstract
Background: Cutaneous melanoma is a kind of skin malignancy with low morbidity but high mortality. Cryptotanshinone (CPT), an important component of salvia miltiorrhiza has potent anti-tumor activity and also indicates therapeutic effect on dermatosis. So we thought that CPT maybe a potential agent for therapy of cutaneous melanoma. Methods: B16F10 and A375 melanoma cells were used for in vitro assay. Tumor graft models were made in C57BL/6N and BALB/c nude mice for in vivo assay. Seahorse XF Glycolysis Stress Test Kit was used to detect extracellular acidification rate and oxygen consumption rate. Si-RNAs were used for knocking down adenosine monophosphate-activated protein kinase (AMPK) expression in melanoma cells. Results: CPT could inhibit the proliferation of melanoma cells. Meanwhile, CPT changed the glucose metabolism and inhibited phosphofructokinase (PFK)-mediated glycolysis in melanoma cells to a certain extent. Importantly, CPT activated AMPK and inhibited the expression of hypoxia inducible factor 1α (HIF-1α). Both AMPK inhibitor and silencing AMPK could partially reverse CPT's effect on cell proliferation, cell apoptosis and glycolysis. Finally, in vivo experimental data demonstrated that CPT blocked the growth of melanoma, in which was dependent on the glycolysis-mediated cell proliferation. Conclusions: CPT activated AMPK and then inhibited PFK-mediated aerobic glycolysis leading to inhibition of growth of cutaneous melanoma. CPT should be a promising anti-melanoma agent for clinical melanoma therapy.
- Subjects
GLUCOSE metabolism; CHINESE medicine; IN vitro studies; GLYCOLYSIS; RESEARCH funding; HERBAL medicine; CELL proliferation; CHALONES; AMP-activated protein kinases; CELLULAR signal transduction; IN vivo studies; TREATMENT effectiveness; MICE; ADENOSINE monophosphate; GENE expression; CELL lines; EXPERIMENTAL design; MEDICINAL plants; ANIMAL experimentation; PSYCHOLOGICAL stress; PHOSPHOTRANSFERASES; BIOLOGICAL assay; EXTRACELLULAR space; OXYGEN consumption; CUTANEOUS malignant melanoma; WARBURG Effect (Oncology); DISEASE progression
- Publication
Chinese Medicine, 2024, Vol 19, Issue 1, p1
- ISSN
1749-8546
- Publication type
Article
- DOI
10.1186/s13020-024-00913-1