In Vitro Induction of Differentiation by Ginsenoside Rh₂ in SMMC‐7721 Hepatocarcinoma Cell Line

Abstract

The aim of this study was to investigate the effects of ginsenoside Rh 2 (G-Rh 2 ) on differentiation of SMMC-7721 hepatocarcinoma cell line in culture. We studied G-Rh 2 -induced differentiation of SMMC-7721 cells through cell proliferation, cell morphology, ultrastructure, cell cycle, cell function and metabolism. The proliferation of treated cells was inhibited, the morphology and ultrastructure seemed normal, the secretory amount and expression of a-foetoprotein, and the specific activity of g-glutamyl transpeptidase, and heat-resistant alkaline phosphatase were all significantly decreased, the secretory amount of albumin and alkaline phosphatase activity were remarkably increased, and the cell was arrested at the G 1 /G 0 phase. Furthermore, G-Rh 2 induced elevated expression of the cyclin-dependent kinase inhibitor p21 WAF1 and p16 INK4a , and declined expressions of cyclin D1 and cyclin E. In addition, G-Rh 2 almost completely inhibited telomerase activity, as measured by polymerase chain reaction-based telomeric repeat amplification protocol coupled with enzyme-linked immune sorbent assay, and human telomerase reverse transcriptase mRNA. Based on these data, it is suggested that G-Rh 2 could induce cell differentiation tending to normal and effectively reduce telomerase activity with affecting transcription levels of human telomerase reverse transcriptase, paralleling the induction of cell differentiation.

Ginsenoside Rh2 inhibits glioma cell proliferation by targeting microRNA-128

“…The ability of Rh2 to suppress cell growth has also been observed in glioma cells [22,23] . Because Rh2 promotes neoplastic cells to return to a normal cell phenotype, it is expected to be a new type of anticancer agent [23] . It displays low toxicity, is associated with only a few side effects and is generally regarded as an anticancer nutrient [23] .…”

“…Because Rh2 promotes neoplastic cells to return to a normal cell phenotype, it is expected to be a new type of anticancer agent [23] . It displays low toxicity, is associated with only a few side effects and is generally regarded as an anticancer nutrient [23] . Although extensive investigations have shown that Rh2 exerts its antiproliferative effects through induction of an apoptotic pathway [24] , the role of miRNAs in this process has not yet been explored.…”

Cholesterol-dependent induction of dendrite formation by ginsenoside Rh2 in cultured melanoma cells

“…To understand the mechanism of action of Rh2, it is worth noting that the latent period before Rh2 manifests its effects on cultured cells is very different for its various effects. For example, it takes more than two days for Rh2 to induce the expression of differentiation markers (7,(16)(17)(18); however, it takes only 3 to 12 h for it to affect the activity of transcription factors (11,19,20). Rh2 affects cdks and cyclins (21), mRNA expression (18), and the phosphorylation level or activity of kinases (11,(22)(23)(24) in less than 60 min.…”

Effects of Rosa roxburghii Extract on Proliferation and Differentiation in Human Hepatoma SMMC-7721 Cells and CD34+ Haematopoietic Cells

“…Low AFP levels indicate that differentiation of hepatoma cells was induced. 17,18) Therefore CT and CiLi may also induce hepatoma cell differentiation.…”