An increase in R2 protein levels and RR activity in KB/M2 cells results in IR resistance, which appears mediated by enhanced IR damage repair during G2. R1 protein overexpression in these isogenic human tumor cells (KB/M1) did not affect RR activity or IR response.

This study investigated the protective effects of a group IIA secretory phospholipase A 2 (sPLA 2 -IIA) inhibitor, ochnaflavone, on the progression of carbon tetrachloride (CCl 4 )-induced acute liver injury in rat liver microsomes in vitro. When rat liver was incubated at 37°C in the presence of CCl 4 , the level of phosphatidylethanolamine (PE) degradation increased markedly compared with the control. The rat 14 kDa platelet PLA 2 antibody, R377, suppressed the degradation of PE. Pretreating the microsome with ochnaflavone (2-16 m mM) reduced the level of PE degradation in a dose dependent manner. In addition, p-bromophenacy bromide (p-BPB), which is a PLA 2 inhibitor, also inhibited PE degradation. However, the inhibitory activity was weaker than that of ochnaflavone. Further investigation showed that ochnaflavone not only inhibited the purified rat platelet sPLA 2 activity in a dose dependent manner with an IC 50 value of 3.45 m mM, when arachidonyl PE was used as a substrate, but also inhibited lipid peroxidation in a dose dependent manner with an IC 50 value of 7.16 m mM. This result suggests that ochnaflavone prevents the progression of CCl 4 -induced PE hydrolysis by inhibiting the endogenous sPLA 2 activity.

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