Mechanism of apoptosis induction associated with ERK1/2 upregulation via goniothalamin in melanoma cells

Abstract

Abstract. The present study aimed to investigate the effect of goniothalamin on apoptosis induction in the A375 melanoma cell line. Melanoma is a type of skin cancer with increased prevalence and no potential standard treatment. Goniothalamin is a plant, bioactive styrly-lactone, which has various bioactivities including anti-microbial, anti-inflammatory and anti-cancer. Apoptosis induction by goniothalamin has been studied in numerous cancer cell lines, however not in the melanoma cell line A375. The results of the MTT assay demonstrated that goniothalamin induced anti-proliferation in a dose dependent manner. Hoechst staining assay demonstrated that goniothalamin induced chromatin condensation and apoptotic bodies in A375 treated cells, and JC-1 staining revealed that goniothalamin induced mitochondrial membrane dysfunction in A375 cells. In addition, goniothalamin decreased the level of anti-apoptotic proteins myeloid cell leukemia 1, B cell lymphoma (Bcl)-2 and Bcl-extra large, whereas it increased the level of pro-apoptotic proteins, Bcl-2 Associated X, apoptosis regulator, t-BID and Bim in A375 treated cells. In addition, goniothalamin also increased active caspase-9, -7 and cleaved-poly (ADP-ribose) polymerase expression in A375 treated cells. Furthermore, phosphorylated (p)-pyruvate dehydrogenase kinase (PDK) 1 (Ser241) and p-RAC-alpha serine/threonine-protein kinase (Akt; Ser473) were decreased, however c-Jun and p-extracellular signal-regulated kinase (ERK)1/2 were increased upon goniothalamin treatment. These results suggest that goniothalamin has an effect, as anti-proliferation and apoptosis induction in A375 cells were associated with upregulated p-ERK1/2, c-Jun and downregulated p-PDK1 (Ser241), p-Akt (Ser473) in A375 cells. Therefore, goniothalamin may be a potential candidate for anti-cancer drug development for melanoma treatment.

Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells

“…Several plant extracts have shown to decrease MMP in a variety of cancer cell lines and this property has also been implicated in the apoptosis and our current results are in consistent with these reports. Furthermore, chromatin condensation is also reported as an indicator of apoptotic nuclei . In the present study, Hoechst staining confirmed the presence of nuclei with bright fluorescence indicating the chromatin condensation and nuclear fragmentation in SC treated HepG2 cells.…”

“…Furthermore, chromatin condensation is also reported as an indicator of apoptotic nuclei. [27][28][29] In the present study, Hoechst staining confirmed the presence of nuclei with bright fluorescence indicating the chromatin condensation and nuclear fragmentation in SC treated HepG2 cells.…”

“…Hepatocyte nuclear factor 1α (HFN‐1α) is a transcription factor that regulates many genes, including albumin, α1‐antitrypsin, and fibrinogen . It has been shown that the expression of HFN‐1α is associated with cancer risk in several tumors, including hepatocellular and pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer . However, recent studies also reported the antitumor potentials of HFN‐1α .…”

“…30 It has been shown that the expression of HFN-1α is associated with cancer risk in several tumors, including hepatocellular and pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer. 29,30 However, recent studies also reported the antitumor potentials of HFN-1α. 31,32 At this juncture, it is not clear whether the downregulation of HFN-1α observed in this study is responsible for apoptosis induction and hence, further studies are warranted on these lines.…”

S100A16suppresses the growth and survival of leukaemia cells and correlates with relapse and relapse free survival in adults with Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukaemia

“…Additionally, we detected elevated levels of ERK1/2 accompanied with the overexpression of S100A16 . ERK1/2 was reported to activate proapoptotic proteins in the BCL2 family and deactivate AKT signalling pathways, leading to apoptosis induction (Tangchirakhaphan et al , ). By suppressing the phosphorylation of ERK1/2, the anti‐proliferation and pro‐apoptosis caused by overexpression of S100A16 could be apparently attenuated.…”