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wt.), RSVL (10mg/kg b.wt.) and RSVL+DOX (10mg/kg +5mg/kg b.wt.) and changes in body weight were observed up to 21 days from the day of treatment.
Evaluation of cell viability and morphological changes in breast cancer cell lines after combination treatment of RSVL and DOX
The cytotoxicity activity of both DOX and RSVL were tested alone at a range of doses in MCF-7 and MDA-MB-231 breast cancer cell lines.
RSVL and DOX combination enhanced DNA fragmentation and chromatin condensation
RSVL and DOX combination markedly reduced wound healing and clonogenic efficiency of breast cancer cells
It could be proposed that the selected synergistic dose of RSVL and DOX were more effective in inhibiting the cell proliferation and invasive properties of breast cancer cell lines (Fig.
For [[.sup.3.H]]-thymidine incorporation and calcium deposition, the maximally stimulated concentration of RSVL was [10.sup.-5] M, whereas RSVL with [10.sup.-4] M turned out to have an inhibitory effect on HBMSCs proliferation and calcium accumulation (Table 1).
Next, the increases of [[.sup.3.H]]-thymidine incorporation, ALP activity and calcium deposition induced by RSVL ([10.sup.-6] M) were abolished by co-incubation with a pure ER antagonist ICI182,780 ([10.sup.-7] M), and [E.sub.2] ([10.sup.-8] M) showed similar effects in the absence or presence of ICI182,780 ([10.sup.-7] M) (Fig.
Effects of RSVL on the activation of ERK1/2 and p38 in HBMSCs cultures
RSVL ([10.sup.-6] M) alone quickly activated both ERK1/2 and p38 activity in 5min in HBMSCs cultures, which lasted about 15min, then returned to basal levels (Fig.
5, both RSVL and [E.sub.2] significantly induced growth and osteoblastic differentiation of HBMSCs, evidenced by an increase of [[.sup.3.H]]-thymidine incorporation as well as ALP activity and calcium deposition.
Concurrent treatment with RSVL or [E.sub.2], SB203580 further increased [[.sup.3.H]]-thymidine incorporation (50% increase, Fig.