Sinomenine hydrochloride inhibits human hepatocellular carcinoma cell growth in vitro and in vivo: Involvement of cell cycle arrest and apoptosis induction

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, therapies against HCC to date have not been completely effective. Sinomenine hydrochloride (SH), an anti‑arthritis drug applied in clinical practice, has been reported to have in vitro anti‑neoplastic activity in various cancer cells. Whether SH inhibits HCC remains unknown. For this purpose, in this study, MTT assay was used to determine cell growth. Flow cytometry, Hoechst staining, DNA fragmentation, western blot analysis, immunohistochemisty and TUNEL staining were performed to investigate the mechanisms involved. The in vivo activity of SH was determined using a mouse xenograft model. SH inhibited the growth of various types of human HCC cells in vitro. We found that SH promoted cell cycle arrest in the G1 phase and sub‑G1 formation, associated with the increased p21/WAF1/Cip1 expression. Additionally, SH induced caspase‑dependent apoptosis, which involved the disruption of mitochondrial membrane potential, the increased release of cytochrome c and Omi/HtrA2 from the mitochondria into the cytoplasm, the downregulation of Bcl‑2 and the upregulation of Bax, the activation of a caspase cascade (caspase‑8, -10, -9 and -3) and PARP, as well as the decreased expression of survivin. The SH‑suppressed growth of human HCC xenografts in vivo occurred due to the decrease in proliferation and the induction of apoptosis, implicating the activation of caspase‑3, the upregulation of p21 and the downregulation of survivin. These findings suggest that SH exhibits anticancer efficacy in vitro and in vivo involving cell cycle and caspase‑dependent apoptosis and may serve as a potential drug candidate against HCC.

MAPK signaling mediates sinomenine hydrochloride-induced human breast cancer cell death via both reactive oxygen species-dependent and -independent pathways: an in vitro and in vivo study

“…15 Sinomenine hydrochloride (SH, Figure 1b), a hydrochloride chemical form of sinomenine, is widely used in clinical treatment of rheumatoid diseases for its anti-inflammatory and anti-immune effects. 16 Recently, its anti-tumor activity has been found in synovial sarcoma, lung cancer and hepatic cancer; 17, 18, 19 however, the molecular mechanisms and the signaling pathways of SH against cancer are still not clarified, and no studies have investigated whether SH could induce breast cancer cell death.…”

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway

“…Sinomenine has attracted great attention for its anti-neoplasm potential. It has been demonstrated to inhibit cell proliferation and induce apoptosis in a variety of human tumor cells (11)(12)(13)(14). Li et al (15) reported that sinomenine induces vasculature normalization that contributes to antitumor and anti-metastasis effect on breast cancer.…”

Sinomenine induces apoptosis in RAW 264.7 cell-derived osteoclasts in vitro via caspase-3 activation

“…Therefore, we hypothesized that SIN could also inhibit bone resorption and the survival of mature osteoclasts by inducing osteoclast apoptosis. Recently, SIN has been shown to modulate caspase activation to induce apoptosis [9,12,13] . However, there is currently no report about the effect of SIN on the apoptosis of osteoclasts.…”

“…We found that SIN can significantly inhibit www.nature.com/aps He LG et al Acta Pharmacologica Sinica npg osteoclastogenesis and resorptive activity in vitro and in vivo (data not shown). Notably, SIN is known to induce apoptosis in various types of cells [9][10][11][12][13][14] . Therefore, we hypothesized that SIN could also inhibit bone resorption and the survival of mature osteoclasts by inducing osteoclast apoptosis.…”