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. 2013 Dec 5;9(12):e1003358. doi: 10.1371/journal.pcbi.1003358

Figure 10. Molecular responses to the BADS112A and LY294002 combination therapy with (red) or without (blue) psychological stress.

Figure 10

The time course ranges from 0 to 8-ADRB2-cAMP-PKA transducing to both S112BAD and CREB (or Mcl1), stimulated by psychological stress are responsible for the drug resistance and synergism pattern switch in drug combination therapy. Psychological stress activated epinephrine-ADRB2-cAMP-PKA signaling pathway, which counteracted the repression of S112BAD by proposed inhibitors and decreased their apoptosis-inducing effects. Independently of S112BAD and S136BAD, the CREB (or Mcl-1) pathway activated by PKA added an anti-apoptotic role.