Metastatic breast cancer remains the leading cause of death in women worldwide. This condition necessitates extensive research to find an effective treatment, one of which is the natural medicine approach. Kaempferia parviflora (KP) is a plant believed to possess anticancer properties. Therefore, this study aims to determine KP’s bioactive compound, cytotoxic, and anti-migration activity in the highly metastatic breast cancer cell line model 4T1, also in the breast cancer cell model MCF-7 and noncancerous cell line NIH-3T3. Maceration with ethanol (EEKP) and infusion with distilled water (EWKP) was used for extraction. The MTT assay was used to test for cytotoxicity, and the scratch wound healing assay was used to test for the inhibition of migration. Phytochemical profiling of EEKP was performed using UHPLC-MS, and the results were studied for in silico molecular docking. Result showed that EEKP had a better cytotoxic activity than EWKP with an IC50 value of 128.33 µg/mL (24 h) and 115.09 µg/mL (48 h) on 4T1 cell line, and 138.43 µg/mL (24 h) and 124.81 µg/mL (48 h) on MCF-7 cell line. Meanwhile, no cytotoxic activity was observed at concentrations ranging from 3–250 µg/mL in NIH-3T3. EEKP also showed anti-migration activity in a concentration of 65 µg/mL. Mass Spectrophotometer (MS) structures from EEKP are 5-Hydroxy-7,4′-dimethoxyflavanone (HDMF), 5-Hydro-7,8,2′-trimethoxyflavanone (HTMF), Retusine, and Denbinobin. The in silico docking was investigated for receptors Bcl-2, Bcl-XL, ERK2, and FAK, as well as their activities. In silico result indicates that HTMF and denbinobin are bioactive compounds responsible for EEKP’s cytotoxic and anti-migration activity. These two compounds and standardized plant extract can be further studied as potential breast cancer treatment candidates.
Breast cancer with Human Epidermal Growth Factor Receptor (HER)2 overexpression increases tumor progession and lead to metastasis, which is primarily cause of mortality in breast cancer. Pentagamaboronon-0 Sorbitol (PGB-0-So) is an aquoeous formulation of curcumin analog, PGB-0, with sorbitol. This compound has been developed as an anti-cancer chemotherapeutic agent and a boron carrying pharmaceutical for boron neutron capture therapy (BNCT). The aims of this study are to investigate antimetastatic activities of PGB-0-So against HER2-overexpressed MCF-7 breast cancer (MCF-7/HER2) cells. The MTT cytotoxicity assay of PGB-0-So exhibited cytotoxic effect with an IC50 value of 35 μM. The testing of anti-migration activity using the scratch wound healing assay demonstrated that PGB-0-So inhibited the closure of the wound on MCF-7/HER2 cells compare to the control. Furthermore, PGB-0-So was able to suppress matrix metalloproteinase (MMP)-9 activities, based on the gelatin zymography assay. In conclusion, PGB-0-So has potency to be developed as an anti-cancer agent against metastatic breast cancer.Keywords : PGB-0-So, anti-metastatsis, cell migration, MMP-9, MCF-7/HER2
The incidence of Breast Cancer Metastasis (MBC) can be categorized in stage IV as well as being the leading cause of death in cases of breast cancer. MBC prognosis is known to be weak, frequent recurrent, and MBC patients have only a survival rate of about 5 years. One of the proteins that causes breast cancer metastasis is Human Epidermal Growth Factor 2 (HER2). Pentagamaboron-0 (PGB-0), a newly curcumin analogue performed cytotoxic effect on HER2-positive breast cancer cells but it is practically water-insoluble. The aims of this study are to determine anti-metastatic activity of a more soluble form of PGB-0 namely PGB-0 fructose complex (PGB-0-F) toward HER2 positive cancer (MCF-7/HER2) cells. PGB-0-F was obtained from Cancer Chemoprevention Research Centre Faculty of Pharmacy Universitas Gadjah Mada. Based on scratch wound healing assay result, PGB-0-F inhibited cell migration especially in combination with doxorubicin at the concentration 15 μM. Under gelatin zymography assay, PGB-0-F in combination with doxorubicin decreased Matrix Metalloproteinases 9 (MMP-9) expression compare to the doxorubicin. Hence, PGB-0-F has a potency to be developed as anti-metastatic agent on HER2 overexpression breast cancer.Keywords : HER2, MCF-7/HER2, PGB-0-F, Metastasis
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