Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity

Cao, Zhifei; Yu, Di; Fu, Shilong; Zhang, Gaochuan; Pan, Yanyan; Bao, Meimei; Tu, Jing; Shang, Bingxue; Guo, Peng-Da; Yang, Ping; Zhou, Quansheng

doi:10.1016/j.toxlet.2013.01.018

Cited by 89 publications

(105 citation statements)

References 61 publications

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“…Uncontrolled tumor cell proliferation and neovascularization are the major causes of malignancy in ovarian cancer. Despite improvements in therapy, the mortality of this disease sustains high and the 5-year overall survival rate are still poor (Cao et al 2013). Thus, looking into the molecular events associated with ovarian cancer is essential.…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical role of TCTP in epithelial ovarian cancer

et al. 2015

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The aim of this study is to investigate the potential role and prognostic significance of translationally controlled tumor protein (TCTP) in human epithelial ovarian cancer (EOC). Western blot was used to evaluate the expression of TCTP in eight fresh EOC tissues. Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections of 119 cases of ovarian cancers. Kaplan-Meier method indicated the relation between TCTP and EOC patients' overall survival rate. Starvation and re-feeding was used to assess cell cycle. Knocking down of TCTP and CCK8 assay showed the role of TCTP in HO8910 cell cycle. We found that TCTP was overexpressed in carcinoma tissues compared with normal tissues. Immunohistochemistry revealed that TCTP expression was significantly associated with clinicopathologic variables. Kaplan-Meier analysis revealed that high TCTP expression was significantly related to poor prognosis of the patients. Starvation and re-feeding suggested TCTP played a critical role in HO8910 cell proliferation. Interference of TCTP and CCK8 assay showed that the TCTP-siRNA treated HO8910 cells grew more slowly than the control group. CCK-8 assays and terminal-deoxynucleoitidyl transferase mediated nick end labeling assays were also performed to demonstrate the cisplatin could inhibit the survival of HO8910 cells and promote their apoptosis. All the experiments we have done showed that TCTP could promote the progression of EOC and reduce the sensitiveness of HO8910 cells to cisplatin.

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Section: Discussionmentioning

confidence: 99%

Expression and clinical role of TCTP in epithelial ovarian cancer

et al. 2015

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“…Evdokimov et al reported that lycorine exhibited cytostatic effects by targeting the actin cytoskeleton rather than by inducing apoptosis in cancer cells [13]. However, lycorine was found to induce apoptosis as well as arrest cell cycle of HL-60, KM3, K562, Hey1B cells in different phases [7,[14][15][16]. Recently, the inhibitory effect on vasculogenic mimicry of melanoma cells [17] and suppression of neovascularization of ovarian cancer Hey1B cells by lycorine were reported [16].…”

Section: Introductionmentioning

confidence: 99%

“…However, lycorine was found to induce apoptosis as well as arrest cell cycle of HL-60, KM3, K562, Hey1B cells in different phases [7,[14][15][16]. Recently, the inhibitory effect on vasculogenic mimicry of melanoma cells [17] and suppression of neovascularization of ovarian cancer Hey1B cells by lycorine were reported [16]. Many factors thus seem involved in the anticancer properties of lycorine and a clear mechanism remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation

et al. 2014

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Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including A549, HCT116, SK-OV-3, NCI-H460, K562, MCF-7 and HL-60. The results indicated that compounds bearing diverse amine substituents at the C-2 position demonstrated good anticancer activities. The selectivity towards different cancer cell lines of the synthesized derivatives is discussed.

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“…Lycorine, a natural alkaloid derived from Amaryllidaceae plants, inhibits growth of various cancers, such as prostate cancer [12], multiple myeloma [13], ovarian cancer [14], lung epithelial cancer [15], leukemia [16–18], and melanoma [19, 20]. The possible mechanisms underlying its anticancer effect was attributed to the induction of cell apoptosis [12, 16, 18] and cell cycle arrest [13, 14, 17] and inhibition of vasculogenic mimicry formation [19].…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma

Wang

et al. 2017

Oncotarget

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Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

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Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity

Cited by 89 publications

References 61 publications

Expression and clinical role of TCTP in epithelial ovarian cancer

Expression and clinical role of TCTP in epithelial ovarian cancer

Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation

Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma

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