Effects of butaclamol, clopenthixol, mepromazine and cannabinol stereoisomers on apoptosis induction

The efflux pump of multidrug resistant mdr cells have different sensitiviti es to some stereoisomeric forms of CNS-active compounds. The ABC transporte rs of mdr cells were more sensitive to (-)butaclamol than to its stereoisom eric counterpart (8), which may function to alter the membrane structure. W e suppose that the drug-accessible membrane structure possesses an importan t role in the induction (or prevention) of apoptosis. Therefore the apoptos is-inducing effect of three stereoisomeric pairs was studied on mouse lymph oma cells. In these experiments levo- and dextromepromazine had similiar ef fects. The cis- and trans-clopenthixol were less effective in apoptosis ind uction than the 12H-benzo(a)-phenothiazine used as a positive control. The effect of stereoisomeric pairs on induced apoptosis was studied when the ce lls were exposed to the stereoisomers for 60 minutes before subjection apop tosis induction by benzo(a)phenothiazine, a well-known apoptosis inducer. T hen the pretreated cells were exposed to 12H-benzo(a)phenothiazine for 60 m inutes. The samples were washed and incubated for 24 hours. The cells were stained with annexin-V FITC and propidium iodine and investigated by flow c ytometry. The mdr cells with increased membrane integrity may resuJt in the preferential killing of multidrug resistant cancer cells in the presence o f some stereoisomers.