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Lp16-PSP, a Member of YjgF/YER057c/UK114 Protein Family Induces Apoptosis and p21WAF1/CIP1 Mediated G1 Cell Cycle Arrest in Human Acute Promyelocytic Leukemia (APL) HL-60 Cells

1
Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning, China
2
Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, Liaoning, China
3
Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(11), 2407; https://doi.org/10.3390/ijms18112407
Received: 23 September 2017 / Revised: 3 November 2017 / Accepted: 7 November 2017 / Published: 13 November 2017
(This article belongs to the Section Biochemistry)
Lp16-PSP (Latcripin 16-Perchloric acid Soluble Protein) from Lentinula edodes strain C91-3 has been reported previously in our laboratory to have selective cytotoxic activity against a panel of human cell lines. Herein, we have used several parameters in order to characterize the Lp16-PSP-induced cell death using human acute promyeloid leukemia (HL-60) as a model cancer. The results of phase contrast microscopy, nuclear examination, DNA fragmentation detection and flow cytometry revealed that high doses of Lp16-PSP resulted in the induction of apoptosis in HL-60 cells. The colorimetric assay showed the activation of caspase-8, -9, and -3 cascade highlighting the involvement of Fas/FasL-related pathway. Whereas, Western blot revealed the cleavage of caspase-3, increased expression of Bax, the release of cytochrome c and decreased expression of Bcl-2 in a dose-dependent manner, suggesting the intrinsic pathway might be involved in Lp16-PSP-induced apoptosis as well. Low doses of Lp16-PSP resulted in the anchorage-independent growth inhibition, induction of G1 phase arrest, accompanied by the increased expression of p21WAF1/CIP1, along with the decreased expression of cyclin D, E, and cdk6. In addition, Lp16-PSP resulted in constitutive translocation inhibition of transcription factor nuclear factor kappa B (NF-κB) into the nucleus by decreasing the phosphorylation of IκBα. All these findings suggested Lp16-PSP as a potential agent against acute promyeloid leukemia; however, further investigations are ultimately needed. View Full-Text
Keywords: Lentinula edodes; Lp16-PSP; acute promyeloid leukemia; extrinsic and intrinsic apoptotic pathway; G1 phase cell cycle arrest; NF-κB signaling pathway Lentinula edodes; Lp16-PSP; acute promyeloid leukemia; extrinsic and intrinsic apoptotic pathway; G1 phase cell cycle arrest; NF-κB signaling pathway
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MDPI and ACS Style

Joseph, T.P.; Chanda, W.; Mohammad, A.F.; Kanwal, S.; Batool, S.; Zhang, M.; Zhong, M.; Huang, M. Lp16-PSP, a Member of YjgF/YER057c/UK114 Protein Family Induces Apoptosis and p21WAF1/CIP1 Mediated G1 Cell Cycle Arrest in Human Acute Promyelocytic Leukemia (APL) HL-60 Cells. Int. J. Mol. Sci. 2017, 18, 2407. https://doi.org/10.3390/ijms18112407

AMA Style

Joseph TP, Chanda W, Mohammad AF, Kanwal S, Batool S, Zhang M, Zhong M, Huang M. Lp16-PSP, a Member of YjgF/YER057c/UK114 Protein Family Induces Apoptosis and p21WAF1/CIP1 Mediated G1 Cell Cycle Arrest in Human Acute Promyelocytic Leukemia (APL) HL-60 Cells. International Journal of Molecular Sciences. 2017; 18(11):2407. https://doi.org/10.3390/ijms18112407

Chicago/Turabian Style

Joseph, Thomson Patrick, Warren Chanda, Abdullah Faqeer Mohammad, Sadia Kanwal, Samana Batool, Meishan Zhang, Mintao Zhong, and Min Huang. 2017. "Lp16-PSP, a Member of YjgF/YER057c/UK114 Protein Family Induces Apoptosis and p21WAF1/CIP1 Mediated G1 Cell Cycle Arrest in Human Acute Promyelocytic Leukemia (APL) HL-60 Cells" International Journal of Molecular Sciences 18, no. 11: 2407. https://doi.org/10.3390/ijms18112407

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