Effect Of Xanthomicrol Research Articles

Comparative Evaluation of Anticancer Activity of Natural Methoxylated Flavones Xanthomicrol and Eupatilin in A375 Skin Melanoma Cells.

Melanoma is a skin cancer caused by the malignant transformation of melanocytes and cutaneous melanoma represents the most aggressive and deadliest type of skin cancer with an increasing incidence worldwide. The main purpose of the present research was to evaluate the anticancer effects of the natural bioactive compounds xanthomicrol (XAN) and eupatilin (EUP) in human A375 malignant skin melanoma cells, a cell line widely used as an in vitro model of cutaneous melanoma. XAN and EUP are lipophilic methoxylated flavones with antioxidant, anti-inflammatory, and antitumor properties. The effects of XAN and EUP on cell viability, morphology, lipid profile, oxidative status, apoptosis, and mitochondrial membrane polarization were determined and compared in A375 cells. At 24 h-incubation (MTT assay), XAN significantly reduced viability at the dose range of 2.5-200 μM, while EUP showed a significant cytotoxicity from 25 μM. Moreover, both methoxylated flavones induced (at 10 and 25 μM, 24 h-incubation) marked cell morphological alterations (presence of rounded and multi-nucleated cells), signs of apoptosis (NucView 488 assay), and a noteworthy mitochondrial membrane depolarization (MitoView 633 assay), coupled to a marked lipid profile modulation, including variations in the ratio of phospholipid/cholesterol and a decrease in the oleic, palmitic, and palmitoleic acid amounts. Moreover, a remarkable time-dependent ROS generation (2',7'-dichlorodihydrofluorescein diacetate assay) was observed during 3 h-incubation of A375 cancer cells in the presence of XAN and EUP (10 and 25 μM). Our results confirm the potential antitumor effect of natural EUP and XAN in cutaneous melanoma by the activation of multiple anticancer mechanisms.

Interaction between cytotoxic effects of Xanthomicrol and Noscapine on PC12 cells

In this study, the cytotoxic effects of methanolic leaf extract of Dracocephalum kotschyii Boiss and methanolic seed extract of Peganum harmala Linn. Alone and in combination, was studied against PC12 and B65 cell lines using MTT assay. In addition, the cytotoxicity of harmine, major $\beta$ indol alkaloid in Peganum harmala was studied against these cells. Furthermore, the cytotoxicity of xanthomicrol, a flavone in methanolic leaf extract of Dracocephalum kotschyii and noscapine, and the interaction between them was also investigated against PC12 cell line. Dracocephalum kotschyii and Peganum harmala and their combination, Spinal-Z, showed cytotoxicity against cell lines tested in a concentration dependent manner. Cytotoxic effects of harmine and xanthomicrol could explain the cytotoxic effect of P. harmala and Dracocephalum kotschyii on these cells. Although, combination of these extracts showed cytotoxicity, but there was a decrease in comparison to each of the extracts alone. P. harmala seeds extract showed a greater preferential cytotoxic effect than D. kotschyii leaves extract on PC12 cells. Such a preferential cytotoxicity was also seen for harmine on the same cell line. Xanthomicrol and noscapine were able to inhibit proliferation of PC12 cells with IC50 of 24.5 µg/mL and 2.8 µg/mL respectively. The cytotoxic effects of xanthomicrrol increased in the presence of noscapine. Flow cytometry analysis showed that xanthomicrol induced apoptosis in HL60 cell lines.