Cancer initiation and progression are mediated through dysregulation of multiple signaling pathways. Specificity protein 1 (Sp1) is a zinc-finger transcription factor that regulates multiple cellular functions and promotes tumor progression by controlling expression of genes involved in cell cycle, apoptosis and DNA damage. In addition, SP1 belongs to the Sp/KLF family of transcription factors. Certainly, the SP1 transcription factor contains a zinc finger protein motif, by which it binds directly to DNA and enhances gene transcription. Increasing evidence suggests that aberrant expression or activity of Sp1 occurs in various cancers types.

Plicamycin (also known as Mithramycin A), a selective specificity protein 1 (Sp1) inhibitor, is antineoplastic antibiotic. Furthermore, it is also a RNA synthesis inhibitor. The main mode of anti-tumor activity of Plicamycin is to inhibit RNA synthesis. According to reports, Plicamycin inhibits binding of Sp1 to promoters, thereby inhibiting proto-oncogenes, anti-apoptotic genes, and pro-angiogenic genes. In addition, Plicamycin reduces the Sp1 protein by inducing proteasome-dependent degradation, thereby inhibiting the growth of cervical cancer through the DR5/caspase-8/Bid signaling pathway. Moreover, in xenograft mouse models of human cervical cancer, Plicamycin shows antitumorigenic activity, can reduce tumor volume and weight, and does not affect body weight. In particular, this compound also significantly inhibits the Sp1 expression in tumor xenografts.

In conclusion, Plicamycin, an antineoplastic antibiotic, is a selective Sp1 inhibitor, which inhibits the growth of various cancers by decreasing Sp1 protein.


[1] Eun-Sun Choi, et al. Sci Rep. 2014 Nov 24;4:7162.

[2] Rajesh R Nair, et al. Leuk Res. 2018 Sep;72:59-66.