Propyl gallate inhibits hepatocellular carcinoma cell growth through the induction of ROS and the activation of autophagy

Abstract

The poor prognosis of hepatocellular carcinoma (HCC) has been attributed to a high frequency of tumor metastasis and recurrence even after successful surgical resection. With less than 30% of patients benefiting from curative treatment, alternative treatment regimens for patients with advanced HCC are needed. Propyl gallate (PG), a synthetic antioxidant used in preserving food and medicinal preparations, has been shown to induce cancer cell death, but the anticancer effects of PG in HCC are unclear. In the present study, we demonstrated that PG inhibited HCC cell proliferation in vitro and in zebrafish models in vivo in a dose- and time-dependent manner. PG also induced cell apoptosis and increased the number of necrotic cells in a time- and dose-dependent manner as determined using a high-content analysis system. We found that PG also increased the intracellular levels of superoxide and reactive oxidative stress as well as the formation of autophagosomes and lysosomes. Regarding the molecular mechanism, PG did not alter the levels of autophagy-related 5 (ATG5), ATG5/12 or Beclin-1 but increased the rate of the LC3-I to LC3-II conversion, suggesting autophagy induction. PG exposure increased the levels of the pro-apoptotic proteins cleaved caspase-3, cleaved PARP, Bax, and Bad and a decreased level of the anti-apoptotic protein Bcl-2. In conclusion, we demonstrate that PG inhibits HCC cell proliferation through enhanced ROS production and autophagy activation. Finally, PG-treated cells induced cell apoptosis and may be a new candidate for HCC therapy.

Extracts of Digested Berries Increase the Survival of Saccharomyces cerevisiae during H2O2 Induced Oxidative Stress

“…For nondigested extracts, the impact on yeast cells was the opposite of that observed for digested extracts, i.e., a decreased stress resistance was observed suggesting a disturbed defence against oxidative stress. This suggestion agrees with the findings reported by Wei et al [ 36 ]. They showed that in human cells the phenolic propyl gallate, synthesized by the condensation of gallic acid and propanol, might, in certain conditions, increase the levels of reactive oxygen species (ROS) and/or promote depletion of protective enzymes or glutathione.…”

“…The health benefits of anthocyanins are commonly suggested to originate from their antioxidant and anti-inflammatory activities related to their chemical structure [ 35 ]. However, epigenetic activities have also been associated with flavonoids, which seem to induce changes in gene expression protecting, for example, against cancer [ 36 ]. The mechanisms of cell protection by polyphenols are not fully understood, and neither is the relative degree of protection by intact anthocyanins versus their derivatives resulting from GI-digestion.…”

miR526b and miR655 Induce Oxidative Stress in Breast Cancer

“…Previously, studies have used a total ROS detection kit for the measurement of ROS and SO in triple negative breast cancer cell lines, colon cancer cells, colorectal cancer cell lines, and in hepatocellular carcinoma cells [17,18,19,20,21]. We used the same ROS-ID Total ROS/SO detection kit (Enzo Life Sciences, Farmingdale, NY, USA) to measure fluorescence due to ROS/SO production following manufacturer’s protocol.…”

Oxidative Stress-Driven Autophagy acROSs Onset and Therapeutic Outcome in Hepatocellular Carcinoma

“…Autophagy inhibitors also foster apoptotic cell death triggered by bevacizumab in the presence of ROS derived from starvation or hypoxia [77]. The occurrence of apoptotic cell death after salinomycin, capsaicin, propyl gallate, or licochalcone A treatment was instead dependent on a direct impact of these molecules on the autophagic response to oxidative stress [78–81] (Table 2).…”