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This study demonstrated that many apoptotic signaling pathways, such as Rho family, PKC family, MAP kinase family, and mitochondria-mediated apoptotic pathway, were triggered by  Lonicera japonica  extracts and irradiation in CH27 cells. Rottlerin, a PKC  δ   -selective inhibitor, reversed the photoactivated  Lonicera japonica  extract-induced decrease in PKC  δ   protein expression and change in cell morphology in this study. In addition, rottlerin inhibited the photoactivated  Lonicera japonica -induced decrease in protein expression of Ras, ERK, p38, PKC  α  , and PKC  ε  , which are the kinases of prosurvival signaling pathway. We also demonstrated that pretreatment with rottlerin prevented actin microfilaments and microtubules from damage during the photoactivated  Lonicera japonica -induced CH27 cell death. Furthermore, the promotion of the cytoskeleton-related signaling cascade following rottlerin by upregulation of cytoskeleton-related mediators (p38, HSP27, FAK, paxillin, and tubulin) and molecules of downstream of F-actin (mitochondria-mediated apoptosis pathway) reduces CH27 cell death, indicating that cytoskeleton is the potential target in the photoactivated  Lonicera japonica extract-induced photokilling of CH27 cells.

Rottlerin InhibitsLonicera japonica-Induced Photokilling in Human Lung Cancer Cells through Cytoskeleton-Related Signaling Cascade