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.

No abstract

Senescence-induced therapy has been improved to increase its cytotoxicity and reduce the resistance of breast cancer cells to chemotherapy agents. An example of a potential senescence-inducing agent is black cumin oil (BCO) because one of its major compounds, α-pinene, can induce senescent cells. This study aims to explore the senescence-inducing activity of BCO in HER2-overexpressing breast cancer cells (MCF7/HER2). The yield obtained from hydro-distillation of BCO was 0.54%, and the main compounds were p-cymene (48.03%), dihydrocarveol (11.39%), and α-pinene (11.29%). BCO exhibited a moderate cytotoxicity profile indicated by IC50, which was >200 μg/mL in both cell lines. In combination with doxorubicin, BCO did not increase the cytotoxicity of doxorubicin. Moreover, BCO induced senescence by increasing 3% of the senescent cells compared with that of the control cells. However, this result was lower than that of the positive control on MCF7/HER2. BCO and doxorubicin combination increased the senescent cells by 3%–7% compared with the positive control on MCF7/HER2 cells. Therefore, the moderate cytotoxicity of BCO could be beneficial to the application of BCO as a supportive agent combined with a chemotherapy drug to increase cancer cells senescent and consequently inhibit cell proliferation.