Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein‐9 and MAPK pathway

Abstract

The effects of Terminalia catappa leaf extracts (TCE) have been widely investigated, including its antioxidative, anti-inflammatory, and antidiabetic activity, as well as its antimetastatic effects on several types of human cancer. However, no study has examined the antimetastatic potential of TCE in cervical cancer cells. This study aimed to elucidate the potential antimetastatic properties of ethanol extracts of Terminalia catappa in 12-O-tetradecanoylphorbol-13-acetate treated human cervical cancer cells and investigate the signaling pathway of this process. We demonstrated that TCE elicited very low cytotoxicity and significantly inhibited cellular migration and invasion in human HeLa and SiHa cervical cancer cells. Moreover, the gelatin zymography, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR analysis revealed that the activity and mRNA level of matrix metalloproteinase-9 (MMP-9) were inhibited by TCE in a concentration-dependent manner.The Western blot results demonstrated that the highest concentration of TCE (100 μg/ml) reduced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) by 46% in the HeLa cell lines. In conclusion, it was revealed that TCE exerted antimetastatic effects on cervical cancer cells by inhibiting the expression of MMP-9 through the ERK1/2 pathway. K E Y W O R D S cervical cancer, MAPK pathway, migration, MMP-9, Terminalia catappa 1 | INTRODUCTION Cervical cancer is one of the leading causes of cancer death and the 4th most frequently occurring malignancy among women worldwide and more than 260 000 women die of cervical cancer annually. 1 Moreover, International Agency for Research on Cancer (IARC) assessed the incidence rate of cervical cancer as 19.0 women per 100 000. 2 Most patients with cervical cancer present with abnormal vaginal bleeding or a cervical mass. 3 Lesion size and pelvic node metastases are vital prognostic factors in cervical cancer. 4 The Chung-Yuan Lee and Shun-Fa Yang contributed equally to the work.

Dioscorea nipponicaMakino suppressesTPA‐induced migration and invasion through inhibition of matrix metalloproteinase‐9 in human cervical cancer cells

“…34 The inhibition of MMP-9 expression effects of Terminalia catappa leaf extracts on cervical cancer cells was also reported. 27 Thus, MMP-9 could be a potential therapeutic target for cervical cancer.…”

“…Numerous studies have speculated that the MAPK signaling is known to regulate MMP-9 expression and play a vital role in cancer metastasis. [27][28][29] Thus, western blotting was used to investigate the effects of DNE on the expression of the MAPK pathway in HeLa cells. The results revealed that DNE significantly diminished the TPA-induced phosphorylation of ERK1/2 ( Figure 4A).…”

RUNX3 Inhibits the Invasion and Metastasis of Human Colon Cancer HT‐29 Cells by Upregulating MMP‐2/9

“…In the process of degradation, large amounts of vascular endothelial growth factors stored in the extracellular matrix can be released to induce tumor angiogenesis and provide the necessary nutritional basis and pathway for tumor cell invasion [25]. MMP-9, also known as Gelatinase B, can degrade and destroy extracellular matrix and basement membrane near the surface of tumor cells, release a large number of growth promoting factors, and make tumor cells invade the surrounding tissues along the missing basement membrane, promoting the invasion and metastasis of tumor cells [26][27][28].…”

Plants of the Genus Terminalia: An Insight on Its Biological Potentials, Pre-Clinical and Clinical Studies

“…Also, leaf ethanol extracts of T. catappa L. from Taiwan was reported by Lee et al. (2019) , who used HeLa and SiHa cervical cancer cell lines to test its antiproliferative effect.…”

“…It was shown that Terminalia sp. extracts have low cytotoxicity and suppress TPA-induced migration and invasion through the inhibition of MMP-9 and ERK1/2 phosphorylation in the cell lines in a dose-dependent manner ( Lee et al., 2019 ). Likewise, water extracts from T. chebula Retz.…”