Abstract
Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.
Highlights
Hepatocellular carcinoma (HCC) is the fifth commonest malignancy and the third commonest cause of cancer mortality [1]
Our study revealed that Xanthium strumarium (XS)-5 and XS-6 significantly induced apoptosis and inhibited cell proliferation by inhibiting the PI3K/AKT/mTOR pathway in HCC
As the invasive property of cancer cells is necessary for the early steps of metastasis, we examined the effects of XS-5 and XS-6 on the invasion of HCC cells using transwell 24-unit invasion assays (Figure 4(b))
Summary
Hepatocellular carcinoma (HCC) is the fifth commonest malignancy and the third commonest cause of cancer mortality [1]. Most of patients with HCC have a poor prognosis because detection of the disease usually occurs at an advanced stage. Patients diagnosed with HCC have a very low survival rate, with about 9% of them surviving for 5 years or less after diagnosis [2]. Despite considerable advances in HCC diagnosis and treatment, the proportion of resectable HCC tumors and cases amenable to liver transplantation remains low. There are no effective curative methods due to the high invasion, early metastasis, and unexpected high recurrence rates of HCC after surgery or interventional treatments such as transcatheter arterial chemoembolization (TACE) [3]. Erefore, it is important to explore alternative strategies that may effectively control HCC. There are a lot of interests in traditional medicines, which is used for cancer monotherapy or in combination with other cancer treatments
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