Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo

Abstract

Cancer metastasis is a major cause of death in cancer patients, with invasion as a first step greatly contributing to the failure of clinical treatments. Any compounds with an inhibitory influence on this process are therefore of prime interest. Momordica charantia (bitter melon) is widely consumed as a vegetable and especially as a folk medicine in Asia. Here, we investigated the anti-invasive effects of bitter melon leaf extract (BMLE) on a rat prostate cancer cell line (PLS10) in vitro and in vivo. The results indicated that nontoxic concentrations of BMLE significantly inhibited the migration and invasion of cells in vitro. The results of zymography showed that BMLE inhibited the secretion of MMP-2, MMP-9 and urokinase plasminogen activator (uPA) from PLS10. Real-time RT-PCR revealed that BMLE not only significantly decreased gene expression of MMP-2 and MMP-9, but also markedly increased the mRNA level of TIMP-2, known to have inhibitory effects on the activity of MMP-2. An EnzChek gelatinase/collagenase assay showed that collagenase type IV activity was partially inhibited by BMLE. In the in vivo study, intravenous inoculation of PLS10 to nude mice resulted in a 100% survival rate in the mice given a BMLE-diet as compared with 80% in the controls. The incidence of lung metastasis did not show any difference, but the percentage lung area occupied by metastatic lesions was slightly decreased in the 0.1% BMLE treatment group and significantly decreased with 1% BMLE treatment as compared with the control. Thus, the results indicate for the first time an anti-metastatic effect of BMLE both in vitro and in vivo. (Cancer Sci 2010; 101: 2234-2240 P rostate cancer is the most common male malignant tumor in Western countries.(1) Androgen ablation therapy is widely used for the initial stage of this disease and may produce favorable outcome, but most patients eventually develop ablationresistant prostate cancers with metastatic foci. Currently, there is no treatment that is able to cure progressive hormone-refractory metastatic prostate cancer.Metastasis is a multi-step process, which involves a series of processes including cellular adhesion and invasion through the basement membrane, transfer via the circulation system, extravasation, and proliferation at a distant site.(2,3) Multiple organ failure caused by multiple metastasis is a major cause of death in cancer patients. Therefore, prevention of tumor metastasis is one primary goal. However, cytotoxic agents have generally been applied for tumor metastasis therapy, with serious sideeffects that can diminish the quality of life of cancer patients. Recently, many efforts have therefore been made to search for non-or low-cytotoxic agents that can reduce the spread of malignant tumors. One focus is on cell invasion using substances in medicinal plants. (5,6) Momordica charantia, or bitter melon, has long been frequently used in various Asian traditional medicine systems and commonly consumed as a vegetable. (7,8) (19) Our previous study showed that the bitter melon ...

Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties

“…We have provided clear evidence that BMLE can exert inhibitory potential against the metastatic properties of PLS10 cells in vitro [72]. Our results pointed to the beneficial effects at non-toxic levels.…”

“…BMLE and kuguacin J exert inhibitory effects in vitro on the progression of androgenindependent rat and human prostate cancer cells, respectively, by suppressing cancer cell invasion and metastasis [72,73]. These provide a basis for the use of BMLE as a dietary supplement and kuguacin J as a broader antineoplastic agent for cancer progression.…”

“…Our studies [60,61,72,73] found that kuguacin J, one of the active compounds contained in MC extracts, exerts anticancer properties in various experimental models, which will be discussed further in the following sections.…”

“…We also have reported the anti cancer abilities of BMLE in vivo [72,73]. Dietary BMLE treatment tended to reduce lung weight and the number of lung metastatic tumors in a model in which intravenous inoculation of androgen-independent rat prostate cancer cells was injected into nude mice, resulting in a 100% incidence of lung metastasis [72].…”

“…Thus, the induction of cell cycle arrest or apoptosis using dietary chemopreventive compounds might be an excellent approach to inhibit the promotion and progression of carcinogenesis and to remove genetically deregulated, premalignant and malignant cells from the body. We have investigated the growth inhibitory effect of BMLE and kuguacin J on androgen-dependent and androgenindependent prostate cancer models [61,72,73].…”