About 67% of cancer survivors who underwent chemotherapy and/or radiotherapy often have self-reported complaints, such as fatigue, depression and cognitive decline. The underlying mechanisms remain elusive. Anti-neoplastic therapy can induce cancer cells senescence, with a concomitant senescence-associated secretory phenotype (SASP). The inflammatory cytokines, proteases and other factors secreted from senescent cancer cells may promote certain damage against surrounding normal cells and activate CD38 expression. CD38 has been identified as the major regulator of cellular NAD⁺ levels. NAD⁺ decline was reported to be highly related to ageing and involves the brain and neurodegenerative diseases. We hypothesized that the mentioned above pathway may lead to neurotoxicity, which may provide a biological explanation towards neuropathy and fatigue syndrome observed in cancer survivors.

Methods:
A549 cell senescence modeling was induced by hydrogen peroxide (H₂O₂). Conditioned media from post-1d and 3d treatment was obtained respectively. Cell senescence phenotype was validated by senescence-associated beta-galactosidase assay, and real-time PCR to determine p16^INK4a, p21 ^waf1/cip1, IL-6, TNF-α, IL-1β, VEGF and IL-10 mRNA levels. Then, the conditioned media was used to treat SHY5Y neuronal cells without serum for 24hr. CD38 hydrolase activity, NAD⁺/NADH ratio, lactate dehydrogenase (LDH) cytotoxicity assay, sulforhodamine B (SRB) assay and mRNA levels of p16^INK4a, p21 ^waf1/cip1, IL-6, TNF-α, IL-1β, VEGF, CD38, PARP1, NF-κB and IL-10 were determined.

Results and conclusion:
Conditioned media obtained from post-3 days hydrogen peroxide treatment was significantly inducing cell-toxicity against SHY5Y cells. Increased CD38 hydrolase activity, CD38 mRNA, p21 ^waf1/cip1mRNA levels of SHY5Y cells was found after exposure to conditioned media. Our data showed that SASP released by senescent A549 cells could induce general neuronal toxicity by in part over-expressing CD38 activity, Studies on the other mechanisms involved are in process.