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

Abstract

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.

LP1 from Lentinula edodes C91-3 Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line SGC-7901

“…Anticancer role of LP13 was revealed by cell cycle arrest at G 1 phase and apoptosis by NF-κB Signaling pathway in A549 cell line [ 17 ]. Lp16-PSP inhibited anchorage-independent growth; p21 WAF1/CIP1 mediated cell cycle arrest at the G 1 phase and apoptosis by the inhibition of NF-κB in leukemia cell line HL-60 [ 18 ].…”

Genomic Regions Associated with Early/Late Feathering in Daheng Broilers Identified Using Genome-Wide Association Studies

“…7A). Similarly, other studies reported that LP16-PSP, Asparagus officialis, and Cordycepin treated cancerous cells i.e., HL-60, human endometrial carcinoma ishikawa cells and leukaemia cells showed changes in mRNA expression of cell cycle related genes (Joseph et al, 2017;Liang et al, 2022;Shi et al, 2022). Scientific reports represented that cell cycle dysregulation cause's inhibition of cell growth or apoptosis and being considered as a marker for chemotherapeutic and chemo preventive agents (Zakaria et al, 2009).…”

“…6B). Previous studies also reported that mRNA expression level of Bax, capase-3, 8, 9, cytochrome-C, and PARP increases while Bcl-2 mRNA expression level was decreased which led the human leukemic cancer, breast cancer and Jurkat T-cell, cervical adenocarcinoma and hepatocellular carcinoma to apoptosis (Joseph et al, 2017;Kiddane et al, 2022;Mbazima et al, 2008;Sun et al, 2018;Zhu et al, 2015). Bcl-2 plays a vital role in apoptosis through maintaining mitochondria in active state.…”

“…LP-7A was also reported possessing antiproliferative characteristics against breast cancer cells (Din et al, 2020). LP-11 and Lp16-PSP was reported as effective against human acute Promyelocytic Leukaemia HL-60 (Gao et al, 2018;Joseph et al, 2017). IC 50 was evaluated for anti-cancer effect of LP-5 protein on various human cancerous and normal cells line which includes (HepG2, A549, H1299, BGC-231, SGC-7901, MDA-MB-231 and MCF-7), and normal cells (HaCat).…”

Polymorphisms of Fatty Acid Synthase Gene and their Association with Milk Production Traits in Chinese Holstein Cows

“…LP-7A was also reported possessing antiproliferative characteristics against breast cancer cells (Din et al, 2020). LP-11 and Lp16-PSP was reported as effective against human acute Promyelocytic Leukaemia HL-60 (Gao et al, 2018;Joseph et al, 2017). IC 50 was evaluated for anti-cancer effect of LP-5 protein on various human cancerous and normal cells line which includes (HepG2, A549, H1299, BGC-231, SGC-7901, MDA-MB-231 and MCF-7), and normal cells (HaCat).…”