Acteoside as a potential therapeutic option for primary hepatocellular carcinoma: a preclinical study

Abstract

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with characteristics of poor prognosis, high morbidity and mortality worldwide. In particular, only a few systemic treatment options are available for advanced HCC patients, and include sorafenib and the recently described atezolizumab plus bevacizumab regimen as possible first-line treatments. We here propose acteoside, a phenylethanoid glycoside widely distributed in many medicinal plants as a potential candidate against advanced HCC. Methods Cell proliferation, colony formation and migration were analyzed in the three human HCC cell lines BEL7404, HLF and JHH-7. Angiogenesis assay was performed using HUVESs. The BEL7404 or JHH-7 xenograft nude mice model was established to analyze the possible antitumor effects of acteoside. qRT-PCR and western blotting were used to reveal the potential antitumor mechanisms of acteoside. Results Acteoside inhibited cell proliferation, colony formation and migration in all the three human HCC cell lines BEL7404, HLF and JHH-7. The prohibition of angiogenesis by acteoside was revealed by the inhibition of tube formation and cell migration of HUVECs. The combination of acteoside and sorafenib produced stronger inhibition of cell colony formation and migration of the HCC cells as well as of angiogenesis of HUVECs. The in vivo antitumor efficacy of acteoside was further demonstrated in BEL7404 or JHH-7 xenograft nude mice model, with an enhancement when combined with sorafenib in inhibiting the growth of JHH-7 xenograft. Further treatment of JHH-7 cells with acteoside revealed an increase in the level of tumor suppressor protein p53 as well as a decrease of kallikrein-related peptidase (KLK1, 2, 4, 9 and 10) gene level with no significant changes of the rest of KLK1–15 genes. Conclusions Acteoside exerts an antitumor effect possibly through its up-regulation of p53 levels as well as inhibition of KLK expression and angiogenesis. Acteoside could be useful as an adjunct in the treatment of advanced HCC in the clinic.

Comparative metabolomics analysis of different sesame (Sesamum indicum L.) tissues reveals a tissue-specific accumulation of metabolites

“…Verbascoside also has been identified in sesame leaves [20]. Acteoside, isoacteoside, and verbascoside possess various pharmacological proprieties, including antiinflammatory, anti-cancer, antioxidative, neuroprotective, anti-diabetes, anti-hypertensive, anti-microbial, and antitumours [52][53][54][55]. Sesamin, one of the major sesame lignan, was detected only in fresh seeds and fresh carpels with the highest relative content in FS.…”

Verbascoside—A Review of Its Antitumor Activities

“…Moreover, VERB + sorafenib showed higher wound healing inhibition than single treatment which indicates the high efficiency of VERB in prevention of cell migration. In the case of angiogenesis, which is linked to tumor growth, progression and metastasis, the inhibition of HUVECs migration, alignment and elongation, and formation of vessel-like structures were also highly efficient with co-treatment [52].…”

Applications of bioactive compounds extracted from olive industry wastes: A review

“…Cardinali et al (2012) reported that verbascoside has a high antioxidant capacity, acting as an effective scavenger of biologically active free radicals and an inhibitor of lipid peroxidation, so that it can be used for treating oxidative stress-related diseases, which may be interesting for application in cosmetics, nutraceuticals, or functional foods. Furthermore, antitumor, antimicrobial, antiinflammatory, anti-thrombotic, and wound healing properties have also been described (Cui et al, 2018;de Moura Sperotto et al, 2018;Ma et al, 2020;Ohno et al, 2002;Qiao et al, 2019;Vertuani et al, 2011). Chen et al (2012) reported that verbascoside (10 mg/kg body weight) has anti-hypertensive activity, lowering both systolic and diastolic blood pressures in hypertensive rats.…”

“…Vertuani et al (2011) demonstrated the stability of verbascoside in suppositories which is an interesting pharmaceutical form to apply in treatment of inflammation of the intestinal mucosa. This compound also presents antitumor activity possibly by increasing p53 levels, as well as by inhibiting KLK expression and angiogenesis, making it a potential candidate for the treatment of advanced hepatocellular carcinoma in the clinic (Ma et al, 2020).…”