The humanin analogue (HNG) prevents temozolomide-induced male germ cell apoptosis and other adverse effects in severe combined immuno-deficiency (SCID) mice bearing human medulloblastoma.

Abstract

Subfertility is a major concern of long-term cancer survivors at the reproductive age. We have previously demonstrated that a potent humanin analogue, HNG, protected chemotherapy-induced apoptosis in germ cells but not cancer cells in a metastatic melanoma allograft model. In this study, we utilized severe combined immuno-deficiency (SCID) mice bearing human medulloblastoma to study the effect of HNG in Temozolomide (TMZ) induced male germ cell apoptosis and white blood cell (WBC) suppression. Human medulloblastoma DAOY cells were injected subcutaneously into the right flank of male SCID mice. Three weeks later, groups of tumor-bearing mice received one of the following treatments: vehicle, HNG, TMZ, or TMZ + HNG. 24 h after last injection, the tumors weights, complete blood counts, liver and spleen weights, male germ cell apoptosis was assessed. HNG did not affect TMZ's significant anti-tumor action. HNG significantly prevented TMZ-induced germ cell apoptosis and attenuated the suppressed total WBC and granulocyte counts in SCID mice with or without TMZ treatment. HNG also attenuated TMZ-induced body weight loss and decrease of spleen and liver weights. In conclusion, HNG ameliorated TMZ-induced germ cell apoptosis; WBC and granulocytes loss; and decreased body/organ weights without compromising the TMZ's anti-cancer action on medulloblastoma xenografts in SCID mice.

• Authors: Yue Jia, Yanhe Lue, Ronald S Swerdloff, Joseph L Lasky, Eduard H Panosyan, Jenny Dai-Ju, Christina Wang
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 109 Pg. 42-50 (08 2019) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 31085184 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Alkylating
• Intracellular Signaling Peptides and Proteins
• humanin
• Temozolomide

Topics

• Animals
• Antineoplastic Agents, Alkylating (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cerebellar Neoplasms (drug therapy, pathology)
• Humans
• Intracellular Signaling Peptides and Proteins (chemistry, pharmacology)
• Liver (drug effects, pathology)
• Male
• Medulloblastoma (drug therapy, pathology)
• Mice, SCID
• Organ Size (drug effects)
• Spermatozoa (cytology, drug effects)
• Spleen (drug effects, pathology)
• Temozolomide (pharmacology)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays (methods)