Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling

Abstract

Praeruptorin A (PA) is a pyranocumarin present in the dried root of Peucedanumpraeruptorum Dunn that has anticancer effects against several types of cells. However, the effect of PA on human cervical cancer cells is unknown. Our results indicate that PA significantly inhibited cell proliferation, colony formation, migration, invasion, and wound closure of HeLa and SiHa cells, induced cell cycle arrest at G0/G1 phase, upregulated Rb, p16, p21 and p27 proteins and downregulated cyclin D1 and S-phase kinase-associated protein 2 (Skp2) proteins. PA also significantly reduced expression of matrix metalloproteinase-2 (MMP-2) and increased expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). In addition, PA suppressed ERK1/2 activation and increased the effect of PD98059 (a specific MEK1/2 inhibitor) in downregulation of MMP-2 and upregulation of TIMP-2. PA treatment inhibited the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on upregulation of ERK1/2 activation, MMP-2 expression, cellular migration, and invasion of HeLa cells. Our findings are the first to demonstrate the activity of PA against cervical cancer cells, and suggest this agent has promise as a therapeutic agent in treatment of human cervical cancer.

Downregulation of Kr�ppel‑like factor 1 inhibits the metastasis and invasion of cervical cancer cells

“…Some other signal molecules (not identified in this study) may also contribute to the regulation the progression of cervical cancer. In addition, our results showed that metastasis-associated antigen MTA was promoted, and that TIMP-2, the specific inhibitor of MMPs ( 33 – 35 ), was inhibited by KLF1 knockdown. Therefore, we confirmed that KLF1 contributed to the inhibition of cervical cancer cell invasion and migration.…”

Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non–Small Cell Lung Cancer through Inactivating ERK/CTSD Signalling Pathways

“…PA has antiproliferative and cytotoxic effects and promotes the inhibitory effects of doxorubincin in human SGC7901 gastric cancer cells [43]. PA inhibits human cervical cancer cell growth and invasion by suppressing MMP-2 expression and ERK1/2 pathway activation [32]. In this study, we investigated the anticancer properties of PA, PB, and PC in NSCLC cells.…”

“…The molecular mechanisms underlying the regulation of cancer progress have been explored with the goal of identifying the complete network of signalling pathways and developing effective approaches against cancers. MAPKs include three major subfamilies, namely ERKs, JNKs, and p38 MAPK, that contribute to the control of cancer development and progression [30][31][32][33]. Huaier Granule extract suppresses proliferation and metastasis in lung cancer cells by downregulating the MTDH, JAK2/STAT3, and MAPK signalling pathways [34].…”

Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma

“…p21, a broad-spectrum CDK inhibitor, has been demonstrated to promote cell cycle arrest by inhibiting the activity of various cyclin-CDK complexes [22,23]. Moreover, some studies have suggested that upregulating p21 expression plays an essential role in G0/G1 arrest [24,25]. Wang et al revealed that TA I inhibited cell cycle progression by decreasing cyclin B and Cdk2 proteins [5].…”