Recent Development of Antitumor Agents from Chinese Herbal Medicines; Part I. Low Molecular Compounds

Tang, Weici; Hemm, Ingrid; Bertram, Barbara

doi:10.1055/s-2003-37718

Cited by 69 publications

(42 citation statements)

References 63 publications

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“…Natural products have been potential sources of novel anticancer drugs over the last few decades (8,9). Many synthetic compounds have been based on key structural features of the bioactive compounds isolated from herbal plants.…”

mentioning

confidence: 99%

CIL-102 Interacts with Microtubule Polymerization and Causes Mitotic Arrest following Apoptosis in the Human Prostate Cancer PC-3 Cell Line

Huang

Guh

et al. 2005

Journal of Biological Chemistry

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There have been no therapeutic agents that provide a survival advantage in hormone-refractory prostate cancer. Recently, the Food and Drug Administration approved docetaxel combined with prednisone for the treatment of patients with advanced metastatic prostate cancer, and it does show a survival benefit. Hence, anti-microtubule drugs might be of benefit in chemotherapy of hormone-refractory prostate cancer. We used metastatic hormone-refractory prostate cancer PC-3 cells to investigate potential molecular mechanisms for CIL-102, a semisynthetic alkaloid derivative. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide and sulforhodamine B assays indicated that CIL-102 inhibits cell growth dose-dependently. Immunofluorescence microscopy and in vitro tubulin assembly assays indicated that CIL-102 binds to tubulin and disrupts microtubule organization. Flow cytometry showed that CIL-102 causes cells to accumulate in G 2 /M phase and sub-G 0 /G 1 phase. CIL-102-induced apoptosis was also characterized by immunofluorescence microscopy. Western blotting and kinase assays showed that CIL-102 exposure induced up-regulation of cyclin B1 and p34 cdc2 kinase activity and olomoucine, a p34 cdc2 inhibitor, profoundly reduced the number of cells accumulated in mitotic phase. Moreover, Bcl-2 phosphorylation, Cdc25C phosphorylation, and survivin expression were increased. CIL-102-induced apoptosis was associated with activation of caspase-3, but a noncaspase pathway may also be involved, since benzyloxycarbonyl-VAD-fluoromethyl ketone, a pancaspase inhibitor, only partially inhibited the apoptosis, and apoptosisinducing factor was translocated from mitochondria to cytosol. We conclude that CIL-102 induces mitotic arrest and apoptosis by binding to tubulin and inhibiting tubulin polymerization. CIL-102 causes mitotic arrest, at least partly, by modulating cyclin-dependent kinases and then apoptosis executed by caspase and noncaspase pathways.

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mentioning

confidence: 99%

CIL-102 Interacts with Microtubule Polymerization and Causes Mitotic Arrest following Apoptosis in the Human Prostate Cancer PC-3 Cell Line

Huang

Guh

et al. 2005

Journal of Biological Chemistry

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“…Comparatively, CnB is easy to express and to purify (42), and the cost of CnB is lower than that of other protein drugs. Unlike some antitumor agents, that have to be extracted from Chinese herbs (43,44), CnB does not have any disadvantages for the environment.…”

Section: Discussionmentioning

confidence: 99%

Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma

et al. 2017

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Abstract. Five-fluorouracil (5-FU) is a widely used chemotherapeutic agent for digestive system tumors; however, continuous use of 5-FU may cause severe side effects, including myelosuppression and immunosuppression. Our previous study revealed that calcineurin B subunit (CnB), an innovative genetic engineering antitumor protein, possesses tumor-suppressive effects with low toxicity. CnB can bind to and activate integrin αM on macrophages, subsequently promoting the expression, and secretion of TNF-related apoptosis-inducing ligand, a specific proapoptotic cytokine. In the present study, whether the combined use of CnB and 5-FU can reverse the myelosuppression, and immunosuppressive effects of 5-FU by reactivating the immune system thus increasing antitumor efficacy, was investigated. It was demonstrated that combined treatment of 5-FU and CnB led to increased tumor-suppressive effects, as indicated by reduced tumor volume and weight when compared with 5-FU or CnB treatment alone in a hepatoma xenograph model. In addition, it was demonstrated that combined treatment inhibited the proliferation of hepatoma cells. Notably, the addition of CnB to 5-FU-based therapy completely reversed the immunosuppressive effect of 5-FU. The spleen index and total number of white blood cells in the combination group were higher compared with that of the 5-FU alone group. Furthermore, pathological examinations indicated that CnB attenuated 5-FU-induced organ damage. Based on these findings, it is proposed that CnB may serve as a novel and promising drug candidate for the improvement of 5-FU-based chemotherapy.

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“…[68][69][70][71][72][73] The poor solubility of this compound encouraged researchers to design analogs with improved physico-chemical characteristics. Indeed, it was found that appending a basic heterocycle side chain onto the lactam nitrogen resulted in significantly better solubility than Meisoindigo while retaining good activity against leukemia K562.…”

Section: The Biological Activity Of Isoindigosmentioning

confidence: 99%

Advances in the synthesis and application of isoindigo derivatives

Богданов¹,

Musin²,

Миронов³

2015

Arkivoc

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Recent Development of Antitumor Agents from Chinese Herbal Medicines; Part I. Low Molecular Compounds

Cited by 69 publications

References 63 publications

CIL-102 Interacts with Microtubule Polymerization and Causes Mitotic Arrest following Apoptosis in the Human Prostate Cancer PC-3 Cell Line

CIL-102 Interacts with Microtubule Polymerization and Causes Mitotic Arrest following Apoptosis in the Human Prostate Cancer PC-3 Cell Line

Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma

Advances in the synthesis and application of isoindigo derivatives

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