Methyl jasmonate represses growth and affects cell cycle progression in cultured Taxus cells

Methyl jasmonate elicitation of Taxus cultures enhances paclitaxel accumulation, but represses growth by inhibition of cell cycle progression. Growth repression is evident both at the culture level and transcriptional level. Methyl jasmonate (MeJA) elicitation is an effective strategy to induce and enhance synthesis of the anticancer agent paclitaxel (Taxol(®)) in Taxus cell suspension cultures; however, concurrent decreases in growth are often observed, which is problematic for large-scale bioprocessing. Here, increased accumulation of paclitaxel in Taxus cuspidata suspension cultures with MeJA elicitation was accompanied by a concomitant decrease in cell growth, evident within the first 3 days post-elicitation. Both MeJA-elicited and mock-elicited cultures exhibited similar viability with no apoptosis up to day 16 and day 24 of the cell culture period, respectively, suggesting that growth repression is not attributable to cell death. Flow cytometric analyses demonstrated that MeJA perturbed cell cycle progression of asynchronously dividing Taxus cells. MeJA slowed down cell cycle progression, impaired the G1/S transition as observed by an increase in G0/G1 phase cells, and decreased the number of actively dividing cells. Through a combination of deep sequencing and gene expression analyses, the expression status of Taxus cell cycle-associated genes correlated with observations at the culture level. Results from this study provide valuable insight into the mechanisms governing MeJA perception and subsequent events leading to repression of Taxus cell growth.