Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo

Abstract

Abstract. Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L and many studies have reported that it exhibits anticancer effects in a number of human tumors. However, there is little information demonstrating the possible effects of emodin on the proliferation and apoptosis of hepatocellular carcinoma (HCC). In the present study, we show that emodin may inhibit the proliferation of SMMC-7721 cells in a dose-and time-dependent manner and induced apoptosis of cells in a concentration-dependent manner after treatment for 24 h. Moreover, we further discovered that the possible molecular mechanisms involved may relate to the mitogenactivated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Emodin may induce the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38 while mildly suppressed the expression of p-c-Jun-N-terminal kinase (p-JNK). However, emodin did not affect the expression of the total (t)-ERK, t-p38 or t-JNK. Furthermore, emodin also suppressed the activation of p-AKT, but not the t-AKT. In vivo, we found that emodin suppressed tumor growth in experimental mice without an obvious change in body weight, which may work through the antiproliferation and apoptosis inducing effects. Moreover, emodin improves the liver and kidney function in mice, revealing that emodin may improve the life quality of the mice with implanted tumors. In conclusion, the above findings indicate that emodin may be a potentially effective and safe drug to induce apoptosis of HCC.

Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma

“…However, CA inhibited PP2A and MEK and ERK were not blocked leading to formation of phosphorylation of ERK counteracting apoptosis. The present finding consistent with those of several studies, which suggest that the activation of ERK or p38 triggers the proliferation and apoptosis of HCC cells . Zhao et al reports that methyl CpG‐binding protein 2 promote the proliferation of HCC cells through ERK1/2 activation and p38 inhibition .…”

Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute Myeloid Leukemia Cells in Vitro and in Vivo

“…A recent study also showed that emodin may suppress hepatocellular carcinoma growth and improve liver and kidney function in experimental mice without an obvious change in body weight, indicating that emodin may be an effective and safe drug for the treatment of hepatocellular carcinoma [31]. To see whether emodin has the potential to improve AML therapy in vivo, we established an AML xenograft mouse model with highly tumorigenic leukemia HL-60/H3 cells.…”

Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase‑dependent pathway

“…1) is a naturally occurring anthraquinone derivative, which is found in a variety of tradition Chinese herbs including Rheum palmatum (9), Polygonum cuspidatum (10), Polygonum multiflorum (11) and Cassia occidentalis (12). Modern pharmacological studies have revealed that emodin possesses anti-proliferative effects on various cancer cells, such as pancreatic cancer (13), breast cancer (14), hepatocellular carcinoma (15), lung carcinoma (16), gastric carcinoma (17) and prostate cancer (18). Furthermore, this drug has also been reported to exhibit antiviral (19), antibacterial (20), anti-allergic (21), anti-osteoporotic (22), anti-diabetic (23), immunosuppressive (24) and neuroprotective (25) activities.…”