A multitude of plants have been used extensively for the treatment of cancers throughout the world. In fact, in many parts of the world especially in poor countries, this may be the only form of cancer therapy. Much research has been focused on the scientific evaluation of traditional anti-cancer drug from the tropical plant, Momordica charantia (MC) which has been used frequently as an anti-cancer agent 1. The green leaves and fruits, the seeds and stems of MC composed of many different proteins and steroids that are chemically active. One such protein is α,β-momorcharin which possesses anti-cancer and anti-HIV properties 2,3. This study investigated the anti-cancer effects and the cellular mechanisms of action of different concentrations of α,β-momocharin (200 µM – 800 µM) on the viability of 1321N1, Gos-3, U87-MG and Weri Rb1, Sk Mel, Corl -23 cancer cell lines compared to normal healthy L6 muscle cell line following incubation for 24 hr using 2500 cells in each 200 µl 96-well plates. The effect of different concentrations (100 µM – 400 µM) of the crude water and methanol soluble extract of MC was also investigated for comparison. The cell viability was measured using MTS assay kit. Caspase-3 activity was measured by caspase kit (Sigma) while cytochrome -c release was measured by cytochrome-c kit (Sigma), respectively for every 8 hr, 16 hr and 24 hr. Initial results have shown that either α, β momocharin or the crude water and methanol soluble extract of MC can evoke significant dose- dependent (P<0.05; Student‘s t-test) decreases in the viability of each cell line tested compared to untreated cells of each cancer cell line. In 1321N1, Gos-3, U87-MG and Weri Rd1, Sk Mel, Corl -23 cell lines, α,β-momorcharin (800 µM) evoked significant (P<0.05) increases in caspase-3 activity compared to untreated cell lines. However, these values were significantly (P<0.05) less than the caspase control value. Similarly, α,β-momorcharin elicited significant (P<0.05) increases in cytochrome-c activity and in intra cellular free calcium concentrations [Ca2+]i in Fura-2 AM loaded cells in the six different cancer cell lines compared to the positive control (normal level). Similar effects were obtained with the crude water and methanol soluble extract employing a dose of (400 µM). In contrast, either α,β-momorcharin or crude extract had no significant effect on cell viability or on the activity of either caspase-3 or cytochrome-c in normal L6 muscle cell line although there was a small increase in [Ca2+]i. Together, the results have indicated that both α,β-momorcharin and crude extract of MC can exert their anti-cancer effect on cancer cell lines by increasing cytochrome -c activity and [Ca2+]i suggesting the involvement of apoptosis in glioma cell death.