Objective:

2

To evaluate the chemical composition and effects of

Artemisia vulgaris

(AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3)

chronic myeloid leu

kemia (K562) and NIH/3T3 fibroblasts.

Methods:

2

Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD

respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM.

Results:

2

HEAV decreased the viability of MCF-7

SKBR-3 and K562 cells (

P

<

0.05). The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts (

P

<

0.05). Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD (

P

<

0.05). The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone (

P

<

0.01). HEAV-induced Ca

2+

release mainly from lysosomes in K562 cells (

P

<

0.01). Furthermore

BAPTA-AM

an intracellular Ca

2+

chelator

decreased the number of non-viable cells treated with HEAV (

P

<

0.05).

Conclusions:

2

HEAV is cytotoxic and activates several modalities of cell death

which are partially dependent on lysosomal release of Ca

2+

. These effects may be related to artemisinin and caffeoylquinic acids

the main compounds identified in HEAV.