Abstract
Breast cancer ranks as a common and severe neoplasia in women with increasing incidence as well as high risk of metastasis and relapse. Translational and laboratory-based clinical investigations of new/novel drugs are in progress. Medicinal plants are rich sources of biologically active natural products for drug development. The 27-kDa trichosanthin (TCS) is a ribosome inactivating protein purified from tubers of the Chinese herbal plant Trichosanthes kirilowii Maximowicz (common name Tian Hua Fen). In this study, we extended the potential medicinal applications of TCS from HIV, ferticide, hydatidiform moles, invasive moles, to breast cancer. We found that TCS manifested anti-proliferative and apoptosis-inducing activities in both estrogen-dependent human MCF-7 cells and estrogen-independent MDA-MB-231 cells. Flow cytometric analysis disclosed that TCS induced cell cycle arrest. Further studies revealed that TCS-induced tumor cell apoptosis was attributed to activation of both caspase-8 and caspase-9 regulated pathways. The subsequent events including caspase-3 activation, and increased PARP cleavage. With regard to cell morphology, stereotypical apoptotic features were observed. Moreover, in comparison with control, TCS- treated nude mice bearing MDA-MB-231 xenograft tumors exhibited significantly reduced tumor volume and tumor weight, due to the potent effect of TCS on tumor cell apoptosis as determined by the increase of caspase-3 activation, PARP cleavage, and DNA fragmentation using immunohistochemistry. Considering the clinical efficacy and relative safety of TCS on other human diseases, this work opens up new therapeutic avenues for patients with estrogen-dependent and/or estrogen-independent breast cancers.
Highlights
Among 145 families of plants, the plant genus Trichosanthes comprises vines which own good potential as the target for anticancer drug discovery [1]
Hep G2 cells served as a positive control for the MTT assay as it has been reported to be inhibited by TCS [36]
MDA-MB-231 and MCF-7 cells were chosen for further studies
Summary
Among 145 families of plants, the plant genus Trichosanthes (family Cucurbitaceae) comprises vines which own good potential as the target for anticancer drug discovery [1] Within this genus, Trichosanthes kirilowii Maximowicz is the most well-known medicinal species for there is a long history for the clinical application as well as experimental studies of its tubers [2]. In the Chinese ethnomedicine T. kirilowii tuber, well-known by its vernacular name ‘Tian Hua Fen’, is considered as a ‘wonder drug’ against some gynecological conditions/illnesses. It was used as an abortifacient and for the treatment of hydatidiform moles, invasive moles, and ectopic pregnancy [2,3,4]. TCS shares remarkable sequence similarity with other antitumor proteins in plant genera
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