Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

Abstract

Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone II A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PI3K, p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.

Tanshinone IIA regulates microRNA‑125b/foxp3/caspase‑1 signaling and inhibits cell viability of nasopharyngeal carcinoma

“…The results showed that the expression levels of IL-18 and IL-1β were markedly increased (Fig. 2F), consistent with the results of a previous study (11). Notably, tanshinone IIA exhibits the opposite effect on normal cells and tumor cells, which may attribute to the different microenvironment.…”

“…Tanshinone IIA inhibits cell proliferation and enhances apoptosis of HK1 cells. Previous studies have demonstrated the anticancer effects of tanshinone IIA in cervical cancer (9,11). In the present study, the effects of tanshinone IIA on HK1 cells were assessed (Fig.…”

“…Tanshinone IIA enhances pyroptotic level of HK1 cells. According to a previous study, HK1 was treated with 8 µM tanshinone IIA for 72 h (11). Considering the potential effects of tanshinone IIA on pyroptosis, it was assessed whether administration of tanshinone IIA regulated pyroptosis in HK1 cells.…”

“…Importantly, treatment with tanshinone IIA significantly suppressed proliferation and induced apoptosis in various cancer cell types, including ovarian cancer (8), cervical cancer (9) and gastric cancer (10). For instance, Tong et al (11) demonstrated that tanshinone IIA could promote the expression of microRNA (miR)-145 and enhance pyroptosis of HeLa cells, resulting in decreased proliferation of these cells. Notably, tanshinone IIA could also downregulate the expression of miR30b and initiate apoptosis in HepG2 cells (12).…”

“…It has been demonstrated that p53 directly enhances lipopolysaccharide (LPS)-induced pyroptosis to markedly decrease tumor growth in A549 cells, suggesting a critical role of p53 in inhibiting tumor growth in patients (14). Notably, a series of studies have focused on the anticancer effects of natural molecules, including tanshinone IIA (11), omega-3 docosahexaenoic acid (15) and paclitaxel (16). However, how tanshinone IIA regulates pyroptosis in NPC cells remains elusive.…”