Abstract
BackgroundKaempferia parviflora (KP) is an herb found in the north of Thailand and used as a folk medicine for improving vitality. Current reports have shown the anti-cancer activities of KP. However, the anti-cancer effects of KP on highly aggressive ovarian cancer have not been investigated. Therefore, we determined the effects of KP on cell proliferation, migration, and cell death in SKOV3 cells.MethodsOvarian cancer cell line, SKOV3 was used to investigate the anti-cancer effect of KP extract. Cell viability, cell proliferation, MMP activity, cell migration, and invasion were measured by MTT assay, cell counting, gelatin zymography, wound healing assay, and Transwell migration and invasion assays, respectively. Cell death was determined by trypan blue exclusion test, AnnexinV/PI with flow cytometry, and nuclear staining. The level of ERK and AKT phosphorylation, and caspase-3, caspase-7, caspase-9 was investigated by western blot analysis.ResultsKP extract was cytotoxic to SKOV3 cells when the concentration was increased, and this effect could still be observed even though EGF was present. Besides, the cell doubling time was significantly prolonged in the cells treated with KP. Moreover, KP strongly suppressed cell proliferation, cell migration and invasion. These consequences may be associated with the ability of KP in inhibiting the activity of MMP-2 and MMP-9 assayed by gelatin zymography. Moreover, KP at high concentrations could induce SKOV3 cell apoptosis demonstrated by AnnexinV/PI staining and flow cytometry. Consistently, nuclear labelling of cells treated with KP extract showed DNA fragmentation and deformity. The induction of caspase-3, caspase-7, and caspase-9 indicates that KP induces cell death through the intrinsic apoptotic pathway. The antitumor activities of KP might be regulated through PI3K/AKT and MAPK pathways since the phosphorylation of AKT and ERK1/2 was reduced.ConclusionsThe inhibitory effects of KP in cell proliferation, cell migration and invasion together with apoptotic cell death induction in SKOV3 cells suggest that KP has a potential to be a new candidate for ovarian cancer chemotherapeutic agent.
Highlights
Kaempferia parviflora (KP) is an herb found in the north of Thailand and used as a folk medicine for improving vitality
Since epidermal growth factor receptor (EGFR), which is highly expressed in ovarian cancer cells, is a very important factor for tumor growth [11], we stimulated SKOV3 cells with Epidermal growth factor (EGF) and performed MTT assay to evaluate whether KP still be able to suppress cell viability
We found that cells treated with KP extract at 0.1 and 0.25 mg/mL significantly increased cell death after 24 h of incubation
Summary
Kaempferia parviflora (KP) is an herb found in the north of Thailand and used as a folk medicine for improving vitality. Ovarian cancer is one of the three common gynecological cancers worldwide after cervical and uterine cancers [1] It is the most leading cause of death among these three gynecologic cancers [2]. The anti-cancer effects of KP against ovarian cancer have not yet been reported This leads us to investigate anti-cancer properties of KP against a high-grade ovarian cancer cell line, SKOV3, which is highly resistant to many cytotoxic agents. Since epidermal growth factor receptor (EGFR), is strongly expressed in ovarian cancer [11] and involved in cell proliferation, cell migration, cell survival, and metastasis, we examined the effects of KP on SKOV3 alone and under the influence of EGF to verify whether KP can overcome the EGF-dependent growth and survival signal transduction pathways. The effects of KP on the PI3K/AKT and MAPK pathways which are important signal transduction pathways for tumorigenesis [12, 13] were defined
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