Abstract
Akebia Fructus has long been used for hepatocellular carcinoma (HCC) in China, while the molecular mechanism remains obscure. Our recent work found that Akebia trifoliate (Thunb.) Koidz seed extract (ATSE) suppressed proliferation and induced endoplasmic reticulum (ER) stress in SMMC-7721. The present study aimed to throw more light on the mechanism. ER stress occurred after ATSE treatment in HepG2, HuH7, and SMMC-7721 cells, manifested as ER expansion, and SMMC-7721 was the most sensitive kind in terms of morphology. Cell viability assay showed that ATSE significantly inhibited cells proliferation. Flow cytometry analysis indicated that ATSE leads to an upward tendency of G0/G1 phase and a reduced trend of the continuous peak after G2/M phase in HepG2; ATSE promoted apoptosis in HuH7 and a notable reduction in G0/G1 phase; ATSE does not quite influence cell cycles of SMMC-7721. Western blot analysis showed an increased trend of the chosen ER stress-related proteins after different treatments but nonsignificantly; only HYOU1 and GRP78 were decreased notably by ATSE in HuH7. Affymetrix array indicated that lots of ER stress-related genes' expressions were significantly altered, and downward is the main trend. These results suggest that ATSE have anticancer potency in HCC cells via partly inducing ER stress.
Highlights
According to the Word Cancer Report from IARC (International Agency for Research on Cancer), human hepatocellular carcinoma (HCC) is the sixth most common malignant cancer throughout the world and the third in China; the cases in China are more than half of the total worldwide [1, 2]
As to SMMC-7721 cells, 0.625 mg/mL ATSE resulted in remarkable endoplasmic reticulum (ER) stress, displayed as different degree of ER expansion (Figure 1(k)); in the combination group (Figure 1(l)), since the ATSE dose was cut by half, the ER stress was comparatively lighter
Akebia Fructus has been long used for HCC in Traditional Chinese medicine MTT (TCM) in China, in the manner of one member in herbal formula under most circumstances
Summary
According to the Word Cancer Report from IARC (International Agency for Research on Cancer), human hepatocellular carcinoma (HCC) is the sixth most common malignant cancer throughout the world and the third in China; the cases in China are more than half of the total worldwide [1, 2]. Most of the anticancer drugs may show severe side effects. Under these circumstances, the need of exploring new drugs in natural products, such as extracts of traditional Chinese herbs, becomes one promising alternative [3, 4]. In China, nearly 80% percent of patients suffering from HCC have taken herbs or herbal compounds to alleviate symptoms, relieve the side effects of radiotherapy or chemotherapy, improve the quality of life, and even extend life span [5,6,7]
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