Cytotoxicity of alkaloids isolated from Peganum harmala seeds.
Peganum harmala is used in traditional medicine to treat a number of diseases including cancer. Our preliminary studies show that the alkaloidal extract of PH seed is cytotoxic to several tumor cell lines in vitro and has antitumor effect in a tumor model in vivo. The present investigation was aimed at extending our previous studies in identifying the components in P. harmala seed-extract responsible for the cytotoxic effects, and study the cytotoxic and antiproliferative activity of isolated alkaloids and total alkaloidal fraction (TAF) in several tumor cell lines. Four alkaloids harmalicidine, harmine, peganine (vasicine) and vasicinone were isolated from the P. harmala seed-extract and their activity and that of TAF were tested a) for their cytotoxic activity against four tumor cell lines three developed by us by chemical-induction in Wistar rats 1) Med-mek carcinoma 2) UCP-med carcinoma 3) UCP-med sarcoma and 4) SP2O-Ag14, and b) for antiproliferative effect on cells of Jurkat, E6-1 clone (inhibition of incorporation of (3)H-thymidine in cellular DNA). The alkaloids and TAF inhibited the growth of tumor cell lines to varying degrees Sp2O-Ag14 was the most sensitive, with IC50 values (concentration of the active substance that inhibited the growth of the tumor cells by 50%) ranging between 2.43 μgmL and 19.20 μgmL, while UCP-med carcinoma was the least sensitive (range of IC50 13.83 μgmL to 59.97 μgmL). Of the substances evaluated, harmine was the most active compound (IC50 for the 4 tumor cell lines varying between 2.43 μgmL and 18.39 μgmL), followed by TAF (range of IC50 7.32 μgmL to 13.83 μgmL) peganine was the least active (IC50 50 μgmL to > 100 μgmL). In terms of antiproliferative effect, vasicinone and TAF were more potent than other substances the concentration of vasicinone, and TAF needed to inhibit the incorporation of (3)H-TDR in the DNA cells of Jurkat, E6-1 clone by 50% (IC50) were 8.60 ± 0.023 μgmL and 8.94 ± 0.017 μgmL, respectively, while peganine was the least active (IC50 >100 μgmL). The IC50 values for harmalacidine (27.10 ± 0.011 μgmL) and harmine (46.57 ± 0.011 μgmL) were intermediate. The harmala alkaloids inhibited the growth of four tumor cell lines, and proliferation of Jurkat cells with varying potencies. Harmine was the most potent in inhibiting cell growth, and vasicinone was most active as antiproliferating substance. The TAF had significant cytotoxic as well as antiproliferating activity.