Cervical cancer is the fourth most lethal human malignancy and the leading cause of death among females around the world. Many antitumor agents have microbial origins. 5'-epi-SPA-6952A is a new 24-membered macrolide isolated from the cultured broth of Streptomyces diastatochromogenes. Therefore, we studied the activity and molecular mechanism of 5'-epi-SPA-6952A in human cervical carcinoma HeLa cell. The results showed that 5'-epi-SPA-6952A significantly inhibited cell proliferation and migration. In addition, 5'-epi-SPA-6952A obviously increased the production of intracellular reactive oxygen species and DNA damage in HeLa cells. Moreover, nuclear shrinkage of cells, decrease in mitochondrial membrane potential, and upregulation of Bax/Bcl-2 ratio resulted in the release of cytochrome c, and activation of caspase-9/3 was observed in HeLa cells treated with 5'-epi-SPA-6952A, which means it enhanced the intrinsic mitochondrial apoptosis. Besides, DNA-damage associated proteins poly (ADP-ribose) polymerase (PARP) and p53 were also studied, and the expressions of cleaved-PARP and p53 were drastically increased in HeLa cells treated with 5'-epi-SPA-6952A. Furthermore, we confirmed that 5'-epi-SPA-6952A affected the survival of HeLa cells by blocking cell cycle progression in the G1 phase. Taken together, the results shows that 5'-epi-SPA-6952A significantly inhibited HeLa cells proliferation via intrinsic mitochondrial apoptosis, cell cycle arrest, and blocking cell migration.
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