Biology subjects

Panachan, J.

Publications and source records attributed to Panachan, J..

2 recordsLinked to original sources

bioRxiv2023

Red blood cell-derived extracellular vesicles with miR-204 mimic loading for pediatric neuroblastoma treatment

Neuroblastoma (NB) is the most common extracranial solid tumor in pediatric population with a high degree of heterogeneity in clinical outcomes, ranging from spontaneous remission to rapid progression and death. Upregulation of a tumor suppressor miR-204 in patient-derived neuroblastoma tumors was associated with good prognosis independent of known risk factors. While miR-204 is recognized as a therapeutic candidate, its delivery was unavailable. This study aimed to develop red blood cell-derived extracellular vesicles (RBC-EVs) as the miR-204 carrier and evaluate the inhibitory activity against neuroblastoma cell lines and spheroids. MiR-204 mimics were loaded into RBC-EVs (RBC-EVmiR-204) by electroporation with the optimized parameters of 250 V, 20 ms, 10 pulsing times. RBC-EVmiR-204, but not the native RBC-EVs, could inhibit cell viability, migration and spheroid formation and growth of MYCN-amp and MYCN non-amplification (MYCN-NA) NB cells, even though the suppressive effects were more preferable in MYCN-amp NB. For the mechanistic insight, SWATH-proteomics suggested that RBC-EVmiR-204 induced dysregulation of ribosomal proteins and alterations in RNA metabolism, leading to inhibiting neuroblastoma progression. This study developed RBC-EVmiR-204 as an alternative/adjunct therapy of pediatric neuroblastoma. The therapeutic efficacy of RBC-EVmiR-204 should be further investigated in preclinical models and clinical studies.

bioengineering↗

bioRxiv2021

AN INTEGRATIVE APPROACH DISCOVERS A NOVEL ANTI-LEUKEMIC PEPTIDE FROM HUMAN MILK

Chemotherapy in childhood leukemia is associated with late morbidity in leukemic survivors, while certain patient subsets are relatively resistant to standard chemotherapy. It is therefore important to identify new agents with sensitivity and selectivity towards leukemic cells, while having less systemic toxicity. Peptide-based therapeutics has gained much attention during the last few years. Here, we used an integrative workflow combining mass spectrometric peptide library construction, in silico anticancer peptide screening, and in vitro leukemic cell studies to discover a novel anti-leukemic peptide having 3+charges and alpha-helical structure, namely HMP-S7, from human breast milk. HMP-S7 showed cytotoxic activity against four distinct leukemic cell lines in a dose-dependent manner but had no effect on solid malignancies or representative normal cells. HMP-S7 induced leukemic cell death by penetrating the plasma membrane to enter the cytoplasm and cause leakage of lactate dehydrogenase, thus acting in a membranolytic manner. Importantly, HMP-S7 exhibited anti-leukemic effect against patient-derived leukemic cells ex vivo. In conclusion, HMP-S7 is a selective anti-leukemic peptide with promise which requires further validation in preclinical and clinical studies. TeaserIn silico screening of naturally occurring human milk peptides discovers a new anticancer peptide that kills leukemic cells in vitro and ex vivo.

pharmacology and toxicology↗