Activation of AMP-activated protein kinase is involved in vincristine-induced cell apoptosis in B16 melanoma cell

Chen, Min-Bin; Shen, Wenxiang; Yang, Yujun; Wu, Xiaoyang; Gu, Jin-Hua; Lu, Pei-Hua

doi:10.1002/jcp.22522

Cited by 82 publications

(67 citation statements)

References 50 publications

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“…Detailed procedures can be found in other studies. 37,38 Briefly, the cells were lysed and the cell lysates were overlaid and incubated in microtiter plate modules coated with anti-Histone antibody. Samples were then incubated with anti-DNA peroxidase followed by color development with ABTS substrate.…”

Section: Caspase-3 Activity Assaymentioning

confidence: 99%

Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against osteosarcoma

Zhu¹,

Min

Fang³

et al. 2015

Cancer Biology & Therapy

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Keywords: MEK/Erk and chemo-resistance, NVP-BEZ235, osteosarcoma, PI3K-Akt-mTOR signaling Abbreviations: mammalian target of rapamycin (mTOR); mTOR complex 1 (mTORC1); mTOR complex 2 (mTORC2); phosphoinositide-dependent protein kinase-1 (PDK1); phosphatidylinositol 3-kinase (PI3K); receptor tyrosine kinases (RTKs).Recent studies have identified that constitutively active phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is an important feature of osteosarcoma, where it promotes cell proliferation, survival, and chemo-resistance. Here, we studied the therapeutic potential of NVP-BEZ235, a novel dual PI3K/mTOR dual inhibitor, on osteosarcoma cells in vivo and in vitro. NVP-BEZ235 was cytotoxic and cytostatic to a panel of osteosarcoma lines (MG-63, U2OS and SaOs-2), where it induce apoptosis and cell-cycle arrest. At the molecular level, NVP-BEZ235 inhibited PI3K-AKT-mTORC1 activation and downregulated cyclin D1/cyclin B1 expressions, while increasing MEK/Erk phosphorylation in osteosarcoma cells. MEK/Erk inhibitors PD98059 and MEK-162 increased NVP-BEZ235 activity on osteosarcoma cells. In vivo, oral NVP-BEZ235 inhibited U2OS xenograft in SCID mice, and its antitumor efficiency was further enhanced by MEK-162 co-administration. Taken together, our findings indicate that dual inhibition of PI3K and mTOR with NVP-BEZ235, either alone or in combination with MEK/Erk inhibitors, may be an efficient treatment for osteosarcoma.

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Section: Caspase-3 Activity Assaymentioning

confidence: 99%

Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against osteosarcoma

Zhu¹,

Min

Fang³

et al. 2015

Cancer Biology & Therapy

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“…Two isoforms are known for catalytic subunit (a1, a2) and they are encoded by different genes (20). Recently, some studies have shown that AMPK plays critical regulatory roles in cancer cell growth and tumorigenesis of cancer cell (21)(22)(23). For example, some research showed that activation of AMPKa1 suppressed the growth of human colon cancer cell (24), whereas some other research showed that AMPKa1 could increases chondrosarcoma cancer cell migration (25), which indicated that AMPKa1 was controversial in different cancer cells.…”

Section: Introductionmentioning

confidence: 99%

miR-148b Functions as a Tumor Suppressor in Pancreatic Cancer by Targeting AMPKα1

Zhao

Zhang

Liu

et al. 2013

Molecular Cancer Therapeutics

110

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miRNAs are small noncoding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-148b has been found in some types of cancer, but its expression and potential biologic role in pancreatic cancer are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 48 pairs of human pancreatic cancer tissues and five cell lines. Furthermore, the deregulated miR-148b was correlated with increased tumor size, late tumor-node-metastasis stage, lymphatic invasion, distant metastasis, and worse prognosis in pancreatic cancer. Functional studies indicated overexpression of miR-148b dramatically suppressed the growth of cancer cells, attributable to induction of apoptosis and cell-cycle arrest at S-phase. Meanwhile, miR-148b remarkably inhibited invasion and enhanced chemosensitivity of pancreatic cancer cells. Moreover, ectopic expression of miR-148b was able to inhibit tumorigenicity in nude mice. Further studies revealed that AMPKa1 might be the direct target gene of miR-148b, and overexpressed AMPKa1 inversely correlated with miR-148b in pancreatic cancer. Silencing of AMPKa1 with RNA interference inhibited the growth of pancreatic cancer cells in vitro and in vivo and also induced apoptosis, cell-cycle arrest, and inhibited invasion of cancer cells, which is consistent with the effects of miR-148b overexpression. In conclusion, miR-148b can inhibit cell proliferation, invasion, and enhance chemosensitivity of pancreatic cancer by targeting AMPKa1. Our present results implicate the potential effects of miR-148b on prognosis and treatment of pancreatic cancer.

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“…AMPK can activate p53 by phosphorylating p53-Ser15 to induce cell cycle arrest and apoptosis (28,29). For example, a combined treatment with metformin and 2-deoxyguanosine, as well as vincristine, an anticancer agent, induced apoptosis in prostate and melanoma cells, respectively, by activating AMPK (30,31). Contrary to these reports, AMPK inhibition resulted in the sensitization of cancer cells to apoptosis by anticancer drugs such as cisplatin as well as metabolic stress such as hypoxia (32,33).…”

Section: Discussionmentioning

confidence: 99%

Anthocyanins in the black soybean (Glycine max L.) protect U2OS cells from apoptosis by inducing autophagy via the activation of adenosyl monophosphate-dependent protein kinase

Choe

et al. 2012

Oncology Reports

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Abstract. Anthocyanins (ATCs) have been reported to induce apoptosis in various types of cancer cells, stimulating the development of ATCs as a cancer chemotherapeutic or chemopreventive agent. It was recently reported that ATCs can induce autophagy, however, the mechanism for this remains unclear. In the present report, we carried out mechanistic studies of the mechanism involved in ATC-induced autophagy using ATCs extracted from black soybeans (cv. Cheongja 3, Glycine max L.). ATCs clearly induced hallmarks of autophagy, including LC3 puncta formation and the conversion of LC3-I to LC3-II in U2OS human osteosarcoma cells. The induction of autophagy was accompanied by the phosphorylation of multiple protein kinases including extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), protein kinase B (AKT) and adenosyl mono phosphate-dependent protein kinase (AMPK). While chemical inhibitors against ERK1/2, p38 MAPK, JNK and AKT failed to inhibit ATC-induced autophagy, the suppression of AMPK by compound C (CC) as well as siRNA against AMPK reduced ATC-induced autophagy. The treatment of ATCs resulted in a decrease in intracellular ATP contents and the activation of AMPK by AICAR treatment also induced autophagy. It is noteworthy that the reduction of autophagy via the inhibition of AMPK resulted in enhanced apoptosis in ATC-treated cells. In addition, siRNA against forkhead box O3A (FOXO3a), a downstream target of AMPK, suppressed ATC-induced autophagy and p27 KIP1 siRNA increased apoptosis in ATC-treated cells. Collectively, it can be concluded that ATCs induce autophagy in U2OS cells via activation of the AMPK-FOXO3a pathway and protect cells from ATC-induced apoptosis via the AMPK-p27 KIP1 pathway. These results also suggest that autophagy-modulating agents could contribute to the efficient development of ATCs as anticancer therapy.

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Activation of AMP-activated protein kinase is involved in vincristine-induced cell apoptosis in B16 melanoma cell

Cited by 82 publications

References 50 publications

Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against osteosarcoma

Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against osteosarcoma

miR-148b Functions as a Tumor Suppressor in Pancreatic Cancer by Targeting AMPKα1

Anthocyanins in the black soybean (Glycine max L.) protect U2OS cells from apoptosis by inducing autophagy via the activation of adenosyl monophosphate-dependent protein kinase

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