Trichosanthin Inhibits Breast Cancer Cell Proliferation in Both Cell Lines and Nude Mice by Promotion of Apoptosis

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.

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

“…TCS has been approved in China for clinical use in gynecology, including ectopic pregnancies, hydatidiform moles, chorionic epithelioma, and abortion. In addition, TCS possesses high antitumor activity that is related to its ribosome-inactivating cytotoxicity, with great promise for cancer therapy [14]. However, like other plant toxins, TCS is poorly cell permeable and with high incident of antigenicity [4,15].…”

SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway

“…SH003 is an extract from Astragalus membranaceus (Am), Angelica gigas (Ag), and Trichosanthes Kirilowii Maximowicz (Tk). The herbal components of SH003 exhibit anti-cancer effects [19, 22, 23], and suppress breast cancer growth [24]. In the present study, we investigated whether SH003 exerts anti-cancer effects on human prostate cancer cells.…”

Hypoglycemic effects of Trichosanthes kirilowii and its protein constituent in diabetic mice: the involvement of insulin receptor pathway

“…For example, trichosanthin is a 27-kDa ribosome inactivating protein that displays abortifacient, anti-viral, and immune-regulatory functions [33]. It also exhibits anti-cancer activities by the induction of apoptosis through G1 arrest, anti-telomerase effects, and anti-metastatic abilities [34, 35]. A serine protease with 46.62 kDa in TK fruits displays a potent anti-colorectal cancer activity by inducing apoptosis via phosphatidylinositol 3′-kinase/Akt-mediated mitochondria-dependent pathway [36].…”