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Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.

ABSTRACT: Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 protein. However, how Sp1 protein is decreased by Mith is not clear. Few studies have investigated the regulation of Sp1 protein by proteasome-dependent degradation as a possible control mechanism for the regulation of Sp1 in cancer cells. Here, we show that Mith decreased Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. We found that prolonged Mith treatment was well tolerated after systemic administration to mice carrying cervical cancer cells. Reduction of body weight was minimal, indicating that Mith was a good therapeutic candidate for treatment of cancers in which Sp1 is involved in promoting and developing disease.

SUBMITTER: Choi ES

PROVIDER: S-EPMC4241519 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.

Choi Eun-Sun ES Nam Jeong-Seok JS Jung Ji-Youn JY Cho Nam-Pyo NP Cho Sung-Dae SD

Scientific reports 20141124

Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 pro ...[more]

PMID: 25418289

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Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.

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Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.

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