Objective: This study intends to explore the potential of galangal extract as a co-chemotherapeutic agent through the analysis of its cytotoxic and migratory effects on metastatic breast cancer cells and as an anti-ageing agent through its senescence inhibitory effect on normal fibroblast cells. Methods: Galangal ethanolic extract (GE) was subjected to a cytotoxicity test with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay alone or in combination with doxorubicin (Dox) against 4T1 cells but not in NIH-3T3 cells. Evidence of senescent cells was detected using a SA-β galactosidase based assay. In addition, the level of reactive oxygen species (ROS), apoptosis, and cell cycle were measured with a flow cytometry-based assay. Meanwhile, cell migration and matrix metalloproteinase (MMP)-9 expression after GE treatment on 4T1 cells were measured using the scratch wound healing assay and gelatin zymography assay, respectively. The metabolomic profiles of GE were traced using gas chromatography-mass spectrometry (GC-MS) analysis. Results: GE effectively inhibited the growth of 4T1 cells with an IC 50 value of 135 µg/mL and increased the cytotoxic effect of Dox at concentrations of 50 and 100 µg/mL. GE increased the number of senescent cells arrested in the G2/M phase but did not cause apoptosis. This effect is compounded by increasing intracellular levels of ROS. However, GE reduced senescence to normal in fibroblast cells (NIH 3T3 cells) under oxidative stress by Dox without any changes in the ROS level. Moreover, GE also inhibited the migration of 4T1 cells and suppressed the expression of MMP-9 induced by Dox. Conclusion: Galangal has the potential for use as a co-chemotherapeutic agent by inducing senescence in correlation with increasing intracellular ROS toward metastatic breast cancer. However, the effect of GE in decreasing the senescence phenomena toward normal fibroblast cells illustrates its potential as a promising anti-ageing agent.
Objectives: This experiment aims to investigate the apoptosis effect of curcumin and its analogs pentagamavunon-0 (PGV-0) and PGV-1 on normal and other cancer cell lines.Methods: Growth inhibition effect was investigated using the MTT method. Double staining used acridine orange, 2-(4-aminodiphenyl)-6-indolcarbamidine dihydrochloride and ethidium bromide was performed to determine morphological changes of cells. Detection of PARP, caspase-3, PUMA and BAX using a western blot method was conducted to elucidate the apoptosis effect of the compounds.Results: PGV-1 (2.5 μM) and PGV-0 (5.0 μM) could inhibit T47D-cell growth on 72 h observation, but not for curcumin. DNA staining showed PGV-1 has the strongest apoptosis induction effect on T47D-cells compared to PGV-0 and curcumin as well. Western blot analysis resulted in cleavage PARP (83 kD) on HeLa, T47D, and MCF-7 cells treated with PGV-1 (2.5 µM), PGV-0 (5.0 µM). Curcumin (10.0 µM) just induced apoptosis on T47D-cell and MCF-7 cell, but not HeLa cell. Cleavage PARP resulted by apoptosis process in the cell. PGV-1 (2.5 µM) had a stronger apoptosis effect compared to PGV-0 (5.0 µM) and curcumin (10.0 µM) based on cleaved PARP result qualitatively. On the normal cell (NH3T3), cells that were treated with the compounds resulted in a negative cleavage PARP. This result indicated that the compounds were part of a selectively induced cancer cell line apoptosis process.
Conclusion:Curcumin, PGV-0 and PGV-1 could inhibit cell growth by induce apoptosis on cancer cells but not on normal cells, which PGV-1 has strongest apoptosis induction effect on cancer cell lines.
Previous research stated that galangal (Alpinia galanga) extract has a potential as cytotoxic agent with active compound of 1’-Acetoxychavicol Acetate (ACA). The objective of this study was to determine the selectivity of ethanol extract, ethyl acetate fraction, and methanol fraction of of galangal, and ACA on cancer cell lines. Cytotoxic activity was carried out using the MTT method on T47D breast cancer, WiDr colon cancer, HeLa cervical cancer, and Vero normal cell lines. The results showed that galangal ethanol extract and its fractions had selectivity index equal to or less than 2 on cancer cells. Meanwhile, ACA had selectivity index more than 3 on T47D cell and HeLa cell. ACA showed a strong cytotoxic activity against cancer cells T47D, HeLa, and WiDr with IC50 values of 3.14, 7.26, and 12.49 μg/ml, respectively. Based on data, it could be concluded that ACA was the most selective to inhibit T47D cell with a selectivity index of 6.6.Keywords: 1’-Acetoxychavicol acetate, galangal (Alpinia galanga), selective index, cytotoxic
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