Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 24 September 2017 / Approved: 25 September 2017 / Online: 25 September 2017 (08:53:12 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2017, 18, 2407
DOI: 10.3390/ijms18112407

Abstract

Lp16-PSP 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 HL-60 as 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 either. 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. Our findings suggest that induction of apoptosis and p21WAF1/CIP1 mediated G1 arrest might be one of the mechanisms of the action of Lp16-PSP, however, further investigations on multiple leukemia cell lines and in vivo models are of ultimate need.

Subject Areas

lentinula edodes; Lp16-PSP; acute promyeloid leukemia; extrinsic and lntrinsic apoptotic pathway; G1 phase cell cycle arrest

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