Frugoside Induces Mitochondria-Mediated Apoptotic Cell Death through Inhibition of Sulfiredoxin Expression in Melanoma Cells

Malignant melanoma is the most life-threatening neoplasm of the skin. Despite the increase in incidence, melanoma is becoming more resistant to current therapeutic agents. The bioactive compound frugoside has been recently reported to inhibit growth when used in various cancer cells. However, this e...

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Bibliographic Details
Published in:Cancers 2019-06, Vol.11 (6), p.854
Main Authors: Song, In-Sung, Jeong, Yu Jeong, Kim, Ji Eun, Shin, Jimin, Jang, Sung-Wuk
Format: Article
Language:English
Subjects:
Animal models
Antioxidants
Antitumor activity
Apoptosis
Binding sites
Bioactive compounds
Cancer therapies
Cell death
Drug dosages
Enzymes
Epidemiology
Gene expression
Kinases
Melanoma
Metastasis
Mitochondria
Neoplasia
Oxidative stress
Proteins
Reactive oxygen species
Signal transduction
Skin
Skin cancer
Toxicity
Xenografts
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Summary:Malignant melanoma is the most life-threatening neoplasm of the skin. Despite the increase in incidence, melanoma is becoming more resistant to current therapeutic agents. The bioactive compound frugoside has been recently reported to inhibit growth when used in various cancer cells. However, this effect has not been demonstrated in melanoma. Here, we found that frugoside inhibited the rate of reduction of hyperoxidized peroxiredoxins (Prxs) by downregulating sulfiredoxin (Srx) expression. Furthermore, frugoside increased the accumulation of sulfinic Prxs and reactive oxygen species (ROS) and stimulated p-p38 activation, resulting in the mitochondria-mediated death of M14 and A375 human melanoma cells. The mitochondria-mediated cell death induced by frugoside was inhibited by the overexpression of Srx and antioxidants, such as N-acetyl cysteine and diphenyleneiodonium. In addition, we observed that frugoside inhibited tumor growth without toxicity through a M14 xenograft animal model. Taken together, our findings reveal that frugoside exhibits a novel antitumor effect based on a ROS-mediated cell death in melanoma cells, which may have therapeutic implications.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11060854