Suppressive effect of maslinic acid on PMA-induced protein kinase C in human B-lymphoblastoid cells.
Protein kinase C (PKC) has been implicated in carcinogenesis and displays variable expression profiles during cancer progression. Studies of dietary phytochemicals on cancer signalling pathway regulation have been conducted to search for potent signalling regulatory agents. The present study was designed to evaluate any suppressive effect of maslinic acid on PKC expression in human B-lymphoblastoid cells (Raji cells), and to identify the PKC isoforms expressed. Effects of maslinic acid on PKC activity were determined using a PepTag assay for non-radioactive detection of PKC. The highest expression in Raji cells was obtained at 20 nM PMA induced for 6 hours. Suppressive effects of maslinic acid were compared with those of four PKC inhibitors (H- 7, rottlerin, sphingosine, staurosporine) and two triterpenes (oleanolic acid and ursolic acid). The IC₅₀ values achieved for maslinic acid, staurosporine, H-7, sphingosine, rottlerin, ursolic acid and oleanolic acid were 11.52, 0.011, 0.767, 2.45, 5.46, 27.93 and 39.29 μM, respectively. Four PKC isoforms, PKC βI, βII, δ, and ζ, were identified in Raji cells via western blotting. Maslinic acid suppressed the expression of PKC βI, δ, and ζ in a concentration-dependent manner. These preliminary results suggest promising suppressive effects of maslinic acid on PKC activity in Raji cells. Maslinic acid could be a potent cancer chemopreventive agent that may be involved in regulating many downstream signalling pathways that are activated through PKC receptors.
Department of Pre-clinical Science, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia. ymlim@utar.edu.my
Lim Yang
LY
Mooi
Wong Teck
WT
Yew
Yap Wei
YW
Hsum
Khoo Kong
KK
Soo
Lim Saw
LS
Hoon
Yeo Chew
YC
Chieng
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000098:Acetophenones / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000187:drug effects / Q000302:isolation & purification; D009828:Oleanolic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects* / Q000201:enzymology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000098:Acetophenones; D016588:Anticarcinogenic Agents; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009828:Oleanolic Acid; D011493:Protein Kinase C; D013110:Sphingosine; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes; D000097245:Ursolic Acid; C412811:maslinic acid; C085746:rottlerin