Abstract
Ivalin, a natural compound isolated from Carpesium divaricatum, showed excellent microtubule depolymerization activities among human hepatocellular carcinoma in our previous work. Here, we investigated its functions on mitochondria-mediated apoptosis in hepatocellular carcinoma SMMC-7721 cells. DAPI (4′,6-diamidino-2-phenylindole) staining, annexin V-fluorexcein isothiocyanate (FITC) apoptosis detection, and western blotting were applied to explore the apoptotic effect of Ivalin. Next, the induction effect of Ivalin on the mitochondrial pathway was also confirmed via a series of phenomena including the damage of mitochondria membrane potential, mitochondria cytochrome c escape, cleaved caspase-3 induction, and the reactive oxygen species generation. In this connection, we understood that Ivalin induced apoptosis through the mitochondrial pathway and the overload of reactive oxygen species. Furthermore, we found that the activation of nuclear factor-κB (NF-κB) and subsequent p53 induction were associated with the apoptotic effect of Ivalin. These data confirmed that Ivalin might be a promising pro-apoptotic compound that can be utilized as a potential drug for clinical treatment.
Highlights
Clinical data have shown that hepatocellular carcinoma (HCC) is the most common and dominating primary tumor with a high incidence rate in adults worldwide [1,2,3]
We found that Ivalin treatment may lead to obviously apoptotic features including apoptotic body formation and nuclear condensation in the same cells
In the presence of an indicated concentration of Ivalin, a significant increase in the proportion of apoptotic cells was observed through double staining by annexin V-fluorexcein isothiocyanate (FITC) and Propidium Iodide (PI)
Summary
Clinical data have shown that hepatocellular carcinoma (HCC) is the most common and dominating primary tumor with a high incidence rate in adults worldwide [1,2,3]. Since many advanced treatments have been used in recent years, chemotherapy is still widely applied to treat HCC in the research of clinical trials [4]. Both the occurrence of drug resistance and recurrences are the key hurdles associated with chemotherapy [5]. Abstracted compounds from plants utilized into an effective anticancer drug is one of the fastest developing therapeutics for chemotherapy [6,7]. It is considered to be an ideal source of effective natural compounds with the structure of sesquiterpenoids, an eudesmane framework [8]. Eudesmane-type sesquiterpenoids and their biological functions including antifungal, Molecules 2019, 24, 3809; doi:10.3390/molecules24203809 www.mdpi.com/journal/molecules
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