Molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in multiple myeloma: a pilot study.

This study explored the molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in human multiple myeloma cell line RPMI8226 cells. RT-PCR and qRT-PCR were used to evaluate the transcriptional levels of Deptor, JNK1, JNK2, JNK3, Raf-1, p53, p21 and NFκB1 at 0, 6, 12, 18, 24 and 48 h after nutrient depletion in RPMI8226 cells. We found that transcriptional levels of Deptor were increased time-dependently at 0, 6, 12 and 18 h, and then decreased. Its alternation was consistent with autophagy. Transcriptional levels of Raf-1, JNK1, JNK2, p53 and p21 were increased time-dependently at 0, 6, 12, 18, 24 and 48 h accompanying with the increase of apoptosis. Transcriptional levels of NFκB1 at 6, 12, 18, 24 and 48 h were decreased as compared with 0 h. It was suggested that all the studied signaling molecules were involved in cellular response to nutrient depletion in RPMI8226 cells. Deptor contributed to autophagy in this process. Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFκB1 may play a possible role in inhibiting apoptosis. It remained to be studied whether Deptor was involved in both autophagy and apoptosis.