Discussion:
From the experiment on the effects of Pimozide, Tamoxifin and Mibefradil on MCF-7 cells, it was concluded that all three drugs significantly inhibit the proliferation of human breast cancer cells grown in culture. All three drugs have cytotoxic effects on these cells at micromolar concentrations; however, Mibefradil exhibited the greatest effect on viability, followed by Pimozide and then Tamoxifin. The pathways of cell death differed for each drug. Mibefradil and Tamoxifin induced the cells to die primarily from necrosis, while Pimozide induced the majority of cells to undergo apoptosis.
In the first experiment, breast cancer cells were grown to contingency in culture. They were then treated with three different concentrations of each drug. At concentrations of 0.10然, 1.0然 and 10然 the cells were treated with Pimozide, Mibefradil and Tamoxifin. After the assay was performed on the cells, the cells were imaged and counted. The total number of dead cells was compared to the original amount of cells, to create percentages of dead cancer cells. At 0.10然, 96% of the original cancer cells treated with Pimozide have died, while 94% of the original cancer cells treated with Mibefradil have died and 88% of the original cancer cells treated with Tamoxifin have died. At 1.0然, 42% of the original cancer cells treated with Pimozide have died, 63% of the original cancer cells treated with Mibefradil have died, and 79% of the original cancer cells treated with Tamoxifin have died. At 10然, 26% of the original cancer cells treated with Pimozide have died, 10% of the original cancer cells treated with Mibefradil have died, and 41% of the original cancer cells treated with Tamoxifin have died. This experiment suggests that the drugs are dose-dependant. At 0.1然 Mibefradil is the most effective, at 1.0然 and 10然, Tamoxifin is the most effective. Overall, Mibefradil seems to be the most dependable, although further experimentation into the optimal dosage for all three drugs would have to be done before a concrete conclusion could be made.
In the second experiment, the pathway of cells death was studied with respect to each drug. The breast cancer cells that were not treated with a drug (the control group) died from both apoptosis and necrosis, in a fairly equal ratio; 6.1% died from apoptosis, while 9.8% died from necrosis. Pimozide seemed to have induced more cells to undergo apoptosis (34%) than necrosis (4.1%). Both Mibefradil and Tamoxifin induced most of the cells to undergo necrosis rather than apoptosis. Thirty-seven percent of the cells treated with Mibefradil died through necrosis, while 3.3% underwent apoptosis. Fifty-six percent of the cells treated with Tamoxifin underwent necrosis, while only 2.1% of those cells underwent apoptosis. It is more effective, with respect to cancer cell death, for a drug to induce apoptosis as opposed to necrosis. Apoptosis is cell death initiated by the internal cell environment, while necrosis is cell death initiated by the external environment. A drug that induces apoptosis would kill the cell internally, without causing a lot of damage to surrounding (potentially healthy) cells. A drug that induces necrosis would damage the environment around the cells, and could potentially kill healthy cells.
This experiment has relevant application to the world of biotechnology because it suggests that the calcium blocking drugs Pimozide and Mibefradil and the estrogen receptor blocking drug Tamoxifin inhibit the proliferation and growth of human breast cancer cells. Cancer is unpredictable and, without detection and proper treatment, can be fatal. This study suggests that Pimozide, Mibefradil and Tamoxifin can induce apoptosis and necrosis in human breast cancer cells grown in culture. Future research could include examining whether calcium channel blocking drugs when used in combination with anticancer estrogen receptor blocking agents can increase breast cancer cell death over and above that observed when used individually.