Dexamethasone enhances trichosanthin-induced apoptosis in the HepG2 hepatoma cell line

Li, Meng; Chen, Fei; Liu, Cuiping; Li, Dongmei; Li, Xiang; Wang, Chong; Li, Jicheng

doi:10.1016/j.lfs.2009.10.016

Cited by 19 publications

(11 citation statements)

References 50 publications

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“…Based on the IC 50 values, MCF-7 and MDA-MB-231 cells were chosen for further study. Hep G2 cells served as a positive control for the MTT assay as it has been reported to be inhibited by TCS [36]. The IC 50 of TCS toward Hep G2 cells was 28.6 µM, a value that corroborated previous reports [36].…”

Section: Resultssupporting

confidence: 78%

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

Fang

Zhang

et al. 2012

PLoS ONE

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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.

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Section: Resultssupporting

confidence: 78%

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

Fang

Zhang

et al. 2012

PLoS ONE

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“…26 In addition, TCS-induced tumor cell apoptosis can be enhanced by dexamethasone through inhibition of the NF-kappaB signaling pathway. 27 In the present study, we demonstrated that TCS inhibited 3LL Lewis lung cancer growth both in vitro and in vivo. Moreover, TCS inhibited tumor growth and prolonged mouse survival more significantly in immunocompetent mice than in immunodeficient nude mice.…”

Section: Discussionsupporting

confidence: 56%

Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM

et al. 2011

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Trichosanthin (TCS), extracted from the Chinese medicinal herb Trichosanthes kirilowi, has shown promise for the inhibition of tumor growth. However, its immunomodulatory effect on tumor-host interaction remains unknown. In this study, we focused on the effect of TCS on murine anti-tumor immune response in the 3LL Lewis lung carcinoma tumor model and explored the possible molecular pathways involved. In addition to inhibiting cell proliferation and inducing apoptosis in the 3LL tumor, TCS retarded tumor growth and prolonged mouse survival more significantly in C57BL/6 immunocompetent mice than in nude mice. This reflected the fact that the host immune system was involved in tumor eradication. Using FACS analysis, we found that TCS increased the percentage of effector T cells, particularly Interferon-gamma (IFN-c) producing CD41 and CD8 1 T cells from tumor-bearing mice. TCS also promoted the vigorous proliferation of antigen-specific effector T cells, markedly increased Th1 cytokine secretion and elicited more memory T cells in tumor-bearing mice, consequently enhancing the anti-tumor response and inducing immune protection. Furthermore, we found that TCS upregulated the expression of tumor suppressor in lung cancer 1 (TSLC1) in 3LL tumor cells and the expression of its ligand, class I-restricted T cell-associated molecule (CRTAM), in effector T cells. Blocking TSLC1 expression with small interfering RNA (siRNA) significantly eliminated the effects of TCS on the proliferation and cytokine secretion of effector T cells, suggesting that TCS enhances anti-tumor immune response at least partially by boosting the interaction between TSLC1 and CRTAM. Collectively, our data demonstrate that TCS not only affects tumor cells directly, but also enhances anti-tumor immunity via the interaction between TSLC1 and CRTAM. These findings may lead to the development of a novel approach for tumor regression.

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“…The present study demonstrated that low concentrations of TCS, compared with the higher concentrations of TCS used in previous studies (10,23,31) assessing antitumor activity suppressed human laryngeal epidermoid carcinoma cell viability and induced apoptosis via the induction of JNK pathway activation. The TCS-induced S-phase cell cycle arrest was partially attributed to the ability of TCS to inhibit cell viability.…”

Section: A B C D Esupporting

confidence: 54%

Low concentrations of trichosanthin induce apoptosis and cell cycle arrest via c-Jun N-terminal protein kinase/mitogen-activated protein kinase activation

Zhang

Chen

Zhou

et al. 2014

Molecular Medicine Reports

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Trichosanthin (TCS) is a type I ribosome--inactivating protein, which inhibits cell viability in human epithelial type 2 (HEp-2) and AMC-HN-8 human laryngeal epidermoid carcinoma cells. Although TCS is a potential chemotherapeutic agent, its mechanism of action remains to be elucidated. In the present study, HEp-2 and AMC-HN-8 cells were treated with different concentrations of TCS combined with or without cisplatin. After 5 days of successive treatment, different experimental groups were detected using a cell counting kit-8 and the collected supernatants were analyzed using a lactate dehydrogenase kit. Flow cytometric assays were performed to detect apoptosis and cell cycle arrest in the HEp-2 and AMC-HN-8 cells, reverse transcription quantitative polymerase chain reaction was performed to detect the levels of p27, p21WAF and western blot analysis was performed to detect changes in c-Jun N-terminal protein kinase (JNK)/phosphorylated (phospho)-JNK, p38/phospho-p38, extracellular signal-regulated kinase (ERK)/phospho-ERK, caspase-3 and caspase-9 in the HEp-2 and AMC-HN-8 cancer cells. TCS significantly inhibited the cell viability of the HEp-2 and AMC-HN-8 cells, independently of necrosis. TCS induced apoptosis and increased the percentage of HEp-2 and AMC-HN-8 cells in the S-phase of the cell cycle. In addition, the JNK/mitogen-activated protein kinase (MAPK) pathway was activated by TCS in the HEp-2 and AMC-HN-8 cells. Low concentrations of TCS also induced apoptosis and S-phase cell cycle arrest in the HEp-2 and AMC-HN-8 cells. The antitumor effects of TCS may be associated with JNK/MAPK activation.

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Dexamethasone enhances trichosanthin-induced apoptosis in the HepG2 hepatoma cell line

Cited by 19 publications

References 50 publications

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

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

Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM

Low concentrations of trichosanthin induce apoptosis and cell cycle arrest via c-Jun N-terminal protein kinase/mitogen-activated protein kinase activation

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