Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

Koshimune, Ryuichiro; Aoe, Motoi; Toyooka, Shinichi; Hara, Fumikata; Ouchida, Mamoru; Tokumo, Masaki; Sano, Yoshifumi; Date, Hiroshi; Shimizu, Nobuyoshi

doi:10.1186/1471-2407-7-8

Cited by 21 publications

(20 citation statements)

References 28 publications

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“…2). These results are consistent with those of previous reports showing that N-BPs are able to inhibit cell proliferation and induce apoptosis in osteoclasts, myeloma, neuroblastoma and lung cancer cells (4,13,16,17).…”

Section: Discussionsupporting

confidence: 83%

Bisphosphonates regulate cell proliferation, apoptosis and pro-osteoclastic expression in MG-63 human osteosarcoma cells

et al. 2012

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Abstract.Bisphosphonates are well established in the management of cancer-induced skeletal complications. Recent studies suggest that nitrogen-containing bisphosphonates (N-BPs) promote the apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To investigate whether N-BPs exhibit a direct antitumor effect on osteoclasts, the current study investigated the effects of zoledronic acid (ZOL) on MG-63 cells in vitro. MG-63 cells were treated with ZOL. The inhibitory effect of ZOL on the growth of MG-63 cells was measured by MTT assay. ZOL-induced apoptosis of the MG-63 cells was examined by Hoechst 33258 staining, electron microscopy, Annexin V-FITC and propidium iodide staining. Reversetranscription polymerase chain reaction (RT-PCR) and western blotting analysis were employed to assess the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL). The MTT assay showed that ZOL induced a distinct dose-and time-dependent reduction of cell viability with an IC 50 value of 52.37±1.0 µM for 72 h. Flow cytometric analysis further revealed that the cell apoptosis was induced by arrest of the cell cycle in the G 1 phase. RT-PCR and western blot analysis demonstrated that ZOL upregulated OPG expression. These results suggest that ZOL has direct effects on osteosarcoma cell growth and apoptosis. Increased OPG expression is an indirect effect, possibly via changes in the local microenvironment.

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Section: Discussionsupporting

confidence: 83%

Bisphosphonates regulate cell proliferation, apoptosis and pro-osteoclastic expression in MG-63 human osteosarcoma cells

et al. 2012

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“…YM529 (1‐Hydroxy‐2‐imidazo [1,2‐a]pyridin‐3‐yl, minodronate) is a newly developed N‐BP which is expected to be useful for the treatment of osteoporosis and hypercalcemia in Japan. Further, YM529 has been reported to show anti‐tumor effects against human cancer cells such as myeloma cells, 14 leukemia cells, 15 renal cell cancer cells, 16 lung cancer cells, 17 and prostate cancer cells 12 both in vitro and in vivo . A second generation BP, pamidronate, was reported to show anti‐tumor effects on HCC cells in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

A novel third generation bisphosphonate, minodronate (YM529), prevented proliferation and migration of hepatocellular carcinoma cells through inhibition of mevalonate pathway

Kogure

Ueno

Kimura

et al. 2009

Hepatology Research

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“…Approximately 80% of lung cancers can be histologically classified as non‐small‐cell lung cancer (NSCLC). The majority of patients present with locally advanced (37%) or metastatic (38%) disease at the time of diagnosis 1. It has been estimated that ∼30–65% of patients with metastatic lung cancer will develop bone metastases 2, 3.…”

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confidence: 99%

The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis

Zarogoulidis

Boutsikou

Zarogoulidis

et al. 2009

Intl Journal of Cancer

116

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Bone metastases occur in 20-40% of patients with lung cancer. Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on lung tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa 1 ), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in lung cancer patients with bone metastases. Lung cancer patients (n 5 144, Stage IV) with evidence of metastasis bone scan were included. Eighty-seven of 144 experienced bone pain and received ZOL, 4 mg i.v. every 21 days (Group A), whereas the other 57 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of docetaxel 100 mg/ m 2 and carboplatin AUC 5 6. It was found that Group A had a statistically significant longer survival (p < 0.01) when compared to Group B. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N-telopeptide of type I collagen (NTx) levels decreased in patients with NTx 29 nM BCE/mM creatinine at baseline after treatment with ZOL. The results of our study suggest that the addition of ZOL increases overall survival in lung cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression. ' 2009 UICC Key words: lung cancer; bone metastasis; bisphosphonates; zoledronic acid; N-telopeptide; type I collagen Lung cancer is the leading cause of death from cancer worldwide. Approximately 80% of lung cancers can be histologically classified as non-small-cell lung cancer (NSCLC). The majority of patients present with locally advanced (37%) or metastatic (38%) disease at the time of diagnosis. 1 It has been estimated that 30-65% of patients with metastatic lung cancer will develop bone metastases. 2,3 Bone metastases cause considerable skeletal morbidity, including bone pain, pathologic fractures, spinal cord compression and hypercalcemia of malignancy. 2 These skeletal-related events (SREs) are the result of the resorption of mineralized bone by osteoclasts. The management of skeletal complications is typically a multimodal endeavor involving surgery, radiation therapy, analgesics and more recently the administration of bisphosphonates (BPs). 4 BPs have been extensively used in the treatment and prevention or palliation of skeletal complications associated with osteolytic lesions in patients with breast cancer, 5 multiple myeloma 6 and more recently in other solid tumors, such as lung cancer.BPs act on bone cells such as osteoclasts and are generally used to treat lytic bone lesions caused by malignancies or bone resorption disorders such as osteoporosis. All BPs are characterized by a phosphorus-carbon-phosphorus (P-C-P)-containing central structure, which promotes the...

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Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

Cited by 21 publications

References 28 publications

Bisphosphonates regulate cell proliferation, apoptosis and pro-osteoclastic expression in MG-63 human osteosarcoma cells

Bisphosphonates regulate cell proliferation, apoptosis and pro-osteoclastic expression in MG-63 human osteosarcoma cells

A novel third generation bisphosphonate, minodronate (YM529), prevented proliferation and migration of hepatocellular carcinoma cells through inhibition of mevalonate pathway

The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis

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