Recent advances in bone-targeted therapies of metastatic prostate cancer

Deng, Xiyun; He, Guangchun; Liu, Junwen; Luo, Feijun; Peng, Xiaoning; Shi-gang, Tang; Gao, Zhiyong; Lin, Qinlu; Keller, Jill M.; Yang, Tao; Keller, Evan T.

doi:10.1016/j.ctrv.2014.04.003

Cited by 48 publications

(34 citation statements)

References 76 publications

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“…Mature osteoclasts cause severe bone resorption by secreting proteases and protons [42,43]. Inhibitors of MMPs and cathepsin K have been considered as promising therapeutic candidates for osteoclast-related diseases [44,45]. ARTD at noncytotoxic concentrations remarkably inhibited RANKL-induced osteoclast formation, mature osteoclast-mediated pit formation, and MMP-9 and cathepsin K secretion from mature osteoclasts.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Artemisinin-Daumone Hybrid Inhibits Cancer Cell-Mediated Osteolysis by Targeting Cancer Cells and Osteoclasts

Taek¹,

Lee²,

Park³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bone metastasis of cancer cells decreases patient survival and quality of life. Hybridization via the covalent coupling of two bioactive natural products is a useful strategy for developing more potent anticancer agents by enhancing their bioavailability and avoiding drug resistance. Methods: The in vivo activities of artemisinin-daumone hybrid 15 (ARTD) were estimated in cancer cell-inoculated mice and ovariectomized mice. The viability, migration, and invasion of cancer cells were measured via MTT, wound-healing, and transwell invasion assays. ARTD-regulated transcription factors were detected with an RT² profiler PCR array kit and Western blotting. Osteoclastogenesis and osteoclast activity were detected with tartrate-resistant acid phosphatase staining, a pit formation assay, gelatin zymography, and a cathepsin K ELISA assay. Results: ARTD blocked cancer-associated osteolysis more potently than artemisinin in mice with intratibially inoculated breast cancer or lung cancer cells. ARTD inhibited the viability, migration, and invasion of breast and lung cancer cells in the absence or presence of transforming growth factor-β1. ARTD treatment induced the expression of tumor suppressive activating transcription factor 3 and inhibited oncogenic E2F transcription factor 1 expression at the mRNA and protein levels. ARTD inhibited receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and bone resorbing activity by reducing the secreted levels of matrix metalloproteinase-9 and cathepsin K. Furthermore, ARTD prevented estrogen deficiency-induced bone loss in ovariectomized mice. Conclusion: ARTD may be a promising candidate for inhibiting cancer-induced bone destruction. The application of ARTD may be extended to patients with chemotherapy-induced ovarian failure or postmenopausal osteoporosis.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Artemisinin-Daumone Hybrid Inhibits Cancer Cell-Mediated Osteolysis by Targeting Cancer Cells and Osteoclasts

Taek¹,

Lee²,

Park³

et al. 2018

Cell Physiol Biochem

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“…SRE cause significant morbidity, reduced performance status, quality of life (QOL) and reduced survival. A reduction in the occurrence of individual SREs with significant decreases in pathological fractures and surgery for bone pain has recently been reported, mainly as the result of bone-targeting treatments [52][53][54]. Hypercalcaemia, which was highly prevalent in breast cancer patients with bone metastases, is currently rarely seen due to a better understanding of the disease and the frequent use of anti-resorptive therapies [52,53].…”

Section: Metastasis To Bonementioning

confidence: 99%

Metastatic Tumors to the Jaws and Mouth

Hirshberg

Berger

Allon

et al. 2014

Head and Neck Pathol

155

171

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Metastatic dissemination to the oral cavity is rare and is usually the evidence of a wide spread disease with an average survival rate of 7 months. In almost a quarter of the cases, oral metastasis was found to be the first indication of an occult malignancy at a distant site. Metastatic lesions can be found anywhere in the oral cavity, however, the jawbones with the molar area is the most frequently involved site. In the oral soft tissues, the gingiva is the most common site, suggesting the possible role of inflammation in the attraction of metastatic deposits. The most common primary malignancies presenting oral metastases were the lung, kidney, liver, and prostate for men, and breast, female genital organs, kidney, and colorectum for women. Most patients with jawbone metastasis complain of swelling, pain, and paresthesia. An exophytic lesion is the most common clinical presentation of metastatic lesions in the oral soft tissues. Early lesions, mainly those located in the gingiva, may resemble a hyperplastic or reactive lesion. Once a lesion is recognized as metastasis, the primary tumor site should be identified following clinical, radiological and histopathological investigations. If standardized diagnostic workup fails to detect the site of origin, then the term carcinoma of unknown primary is applied. Personalized medicine tools such as tissue-oforigin assays should be applied, either by immunohistochemical testing or by molecular-profiling methods as these may lead to a more favorable outcome.

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“…For PrCa patients, the aggressive metastatic disease reflects the most adverse clinical outcome and is difficult to study given the heterogeneous nature of this malignant tumor (2,3). At metastatic sites, predominantly bone, altered interaction with the prostate microenvironment promotes the ability of tumor cells to migrate (4,5). Understanding the molecular events involved in the development of metastatic PrCa has the potential to identify new biological targets that can aid in prognosis and development of more effective therapies.…”

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confidence: 99%

“…Overexpression of ␣ v ␤ 6 , an epithelium-specific integrin, has been reported to correlate with malignant progression and poor clinical prognosis in a variety of carcinomas, and to promote metastasis (17,18). ␣ v ␤ 6 expression is not detectable in normal human prostate but is highly expressed in human primary PrCa (19), 4 as well as murine PrCa in Pten pcϪ/Ϫ mice (20) and thus, is a promising therapeutic target in PrCa. Furthermore, this integrin has * This work was supported, in whole or in part, by National Institutes of Health multiple regulatory functions in tumor cell biology.…”

mentioning

confidence: 99%