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The methanol and fractionated extracts (hexane, ethyl acetate and water) of Alpinia mutica (Zingiberaceae) rhizomes were investigated for their cytotoxic effect against six human carcinoma cell lines, namely KB, MCF7, A549, Caski, HCT116, HT29 and non-human fibroblast cell line (MRC 5) using an in vitro cytotoxicity assay. The ethyl acetate extract possessed high inhibitory effect against KB, MCF7 and Caski cells (IC50 values of 9.4, 19.7 and 19.8 µg/mL, respectively). Flavokawin B (1), 5,6-dehydrokawain (2), pinostrobin chalcone (3) and alpinetin (4), isolated from the active ethyl acetate extract were also evaluated for their cytotoxic activity. Of these, pinostrobin chalcone (3) and alpinetin (4) were isolated from this plant for the first time. Pinostrobin chalcone (3) displayed very remarkable cytotoxic activity against the tested human cancer cells, such as KB, MCF7 and Caski cells (IC50 values of 6.2, 7.3 and 7.7 µg/mL, respectively). This is the first report of the cytotoxic activity of Alpinia mutica.

The aims of this study were to investigate the combined effects of a natural compound 1 0 S-1 0 -acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose-and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 + 0.01 and 0.85 + 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.

1’-(S)-1’-Acetoxychavicol acetate (ACA) isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff. was investigated for its potential as an anticancer drug. In this communication, we describe the cytotoxic and apoptotic properties of ACA on five human tumour cell lines. Data from MTT cell viability assays indicated that ACA induced both time- and dose-dependent cytotoxicity on all tumour cell lines tested and had no adverse cytotoxic effects on normal cells. Total mortality of the entire tumour cell population was achieved within 30 hrs when treated with ACA at 40.0 µM concentration. Flow cytometric analysis for annexin-V and PI dual staining demonstrated that cell death occurred via apoptosis, followed by secondary necrosis. The apoptotic effects of ACA were confirmed via the DNA fragmentation assay, in which consistent laddering of genomic DNA was observed for all tumour cell lines after a 24 hrs post-treatment period at the IC50 concentration of ACA. A cell cycle analysis using PI staining also demonstrated that ACA induced cell cycle arrest at the G0/G1 phase, corresponding to oral tumour cell lines. In conclusion, ACA exhibits enormous potential for future development as a chemotherapeutic drug against various malignancies.

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From the rhizomes of Kaempferia galanga, ethyl cinnamate (EC) was isolated and its vasorelaxant effect was examined on the rat aorta. EC inhibited the tonic contractions induced by high K+ and phenylephrine (PE) in a concentration-dependent manner, with respective IC50 values of 0.30 +/- 0.05 mM and 0.38 +/- 0.04 mM. The relaxant effect against PE-induced contractions was greater in the presence of endothelium. Pre-treatment of the aorta with methylene blue and indomethacin significantly reduced the relaxant effect. These results suggest that the inhibitory effects of EC may involve inhibition of Ca2+ influx into vascular cells and release of nitric oxide (NO) and prostacyclin from the endothelial cells. Thus, the vasorelaxant effect of EC mediated through multiple pathways may explain the traditional use of the parent plant in treating hypertension.