Effect of α, β momorcharin on viability, caspase activity, cytochrome c release and on cytosolic calcium levels in different cancer cell lines

Abstract

A multitude of plants have been used extensively for the treatment of cancers throughout the world. The protein, α, β momorcharin has been extracted from the plant Momordica charantia (MC), and it possesses anti-cancer and anti-HIV properties similar to the crude water and methanol soluble extract of the plant. This study investigated the anti-cancer effects and the cellular mechanisms of action of α, β momocharin (200-800 μM) on 1321N1, Gos-3, U87-MG, Sk Mel, Corl-23 and Weri Rb-1 cancer cell lines compared to normal healthy L6 muscle cell line measuring cell viability using MTT assay kit, Caspase-3 and 9 activities, cytochrome c release and intracellular free calcium concentrations [Ca(2+)]i. The results show that α, β momorcharin can evoke significant dose-dependent (P < 0.05; Student's t test) decreases in the viability (increases in cell death) of 1321N1, Gos-3, U87-MG, Sk Mel, Corl-23 and Weri Rb-1 cancer cell lines compared to healthy L6 muscle cell line and untreated glioma cells. α, β momorcharin (800 μM) also evoked significant (P < 0.05) increases in caspase-3 and 9 activities and cytochrome c release. Similarly, α, β momorcharin elicited significant (P < 0.05) time-dependent elevation in [Ca(2+)]i in all five glioma cell lines compared to untreated cells. Together, the results have demonstrated that α, β momorcharin can exert its anti-cancer effect on different cancer cell lines by intracellular processes involving an insult to the mitochondria resulting in cellular calcium over loading, apoptosis, cytochrome release and subsequently, cell death.

Food prospects and nutraceutical attributes of Momordica species: A potential tropical bioresources – A review

“…Xiong et al [62] isolated a novel ribosome-inactivating protein called ␣-momorcharin and ␤-momorcharin from the mature seeds of M. charantia which efficiently inhibits the growth of prostate cancer. Manoharan et al [63] described the mechanisms of this phytochemical in different cancer cell lines, ␣-momorcharin and ␤-momorcharin increased the cell death specifically in cancer cell lines by increasing the caspase-3 and 9 activities, releasing cytochrome c and elevating calcium level. Recently, Weng et al [44] isolated a novel cucurbitane-type triterpenoid (3β, 7β-dihydroxy-25-methoxycucurbita-5, 23-diene-19-al) from wild bitter gourd that induces apoptotic death in breast cancer cells.…”

Bitter melon: a panacea for inflammation and cancer

“…Manoharan et al . have shown that α- and β -momocharin treatment reduces the cell viability (increases in cell death) of 1321N1, Gos-3, U87-MG, Sk-Mel, Corl-23 and Weri Rb-1 cancer cell lines as compared to healthy L6 muscle cell line and untreated glioma cells [88] . Fang et al have purified and characterized a 14-kDa Ribonucleases (RNase MC2) from the seeds of MC.…”

Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties

“…c-Jun N-terminal kinases (JNKs) signal pathway, which relates to cell apoptosis, was also triggered by α-MMC [83]. Many studies demonstrated that α-MMC involved in similar pathways with TCS, such as caspase-3 and 9 activations and interaction with low density lipoprotein receptor-related protein 1 (LRP1) [83,84]. LRP1 plays a vital role in the cytotoxicity mechanism of α-MMC because α-MMC mediated cytokine expression and MAPK pathway, which would be hindered by LRP1 silencing.…”