Isocordoin analogues promote apoptosis in human melanoma cells via Hsp70

Abstract

Isocordin 1 and a series of 4‐oxyalkyl‐isocordoin analogues 2–8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC50 values of 12.91 ± 0.031, 24.88 ± 0.013, and 11.62 ± 0.017, respectively. These analogues, 4, 5, and 6, also induced an apoptotic response at 12.5‐ and 25‐μM concentrations. They inhibited the expression of antiapoptotic proteins Bcl‐2 and Hsp70, a critical factor that promotes tumour cell survival. In contrast, Bax and caspase‐9 expression, and caspase‐3 enzyme resulted activated. These results were correlated to a DNA fragmentation typical of apoptosis and an increase of intracellular reactive oxygen species (ROS) levels. Alternatively, at higher concentration (50 μM), when the capacity of the cells to sustain Hsp70 synthesis is reduced, our results seem to indicate that necrosis was induced by a further increase in ROS production. Therefore, the central finding in the present study is that these molecules downregulates Hsp70 expression. Altogether, these results suggest that 4‐oxyalkyl‐isocordoin analogues 4, 5, and 6 deserve to be deeply investigated for a possible application as Hsp70 inhibitor in the management of melanoma.

The Effect of Ginger Supplementation on the Improvement of Dyspeptic Symptoms in Patients With Functional Dyspepsia

“…In another study, 24 patients with FD were randomized to receive either ginger or a placebo for 14 days. The study found that ginger significantly improved gastric emptying compared to a placebo [ 19 ]. However, a study involving 14 healthy adults found no significant effect of ginger on gastric emptying.…”

“…The study included 60 patients who were randomized to receive either ginger or a PPI for four weeks. Both treatments were effective in reducing symptoms of dyspepsia, including epigastric discomfort, with no significant difference between the two groups [ 19 ]. A report from a systematic review of randomized controlled trials (RCTs) found that ginger was more effective than a placebo in reducing symptoms of dyspepsia, including epigastric discomfort.…”

Alarmins in cutaneous malignant melanoma: An updated overview of emerging evidence on their pathogenetic, diagnostic, prognostic, and therapeutic role

“…In melanoma, circulating heat shock protein 70 (HSP70) as the primary effector of NLRP3 triggering a distant TLR4‐dependent signaling cascade (NLRP3‐HSP70‐TLR4 axis), regulates granulopoiesis and recruitment and the accumulation of PMN‐MDSCs in distant organs, thus supporting the creation of a premetastatic niche 23 . Furthermore, in the context of the well‐investigated anti‐apoptotic role in melanoma cells of HSP70, 24 the 78 kDa cell surface glucose‐regulated protein (csGRP78), as a member of the HSP70 family, is involved in autoimmune‐mediated activation of signaling pathways promoting cancer cell survival 25 . Concerning the presumed HSP90 role in melanoma, the scientific literature to date has been inconclusive.…”