Lophira Alata Suppresses Glioblastoma Cell Growth via Inhibition of Protein Kinase C-α
Type of Submission
Poster
Keywords
Lophira alata, malignant glioma, antiproliferative effects, MTT assay, gene silencing
Proposal
The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in malignant brain tumor cells. This study was aimed at examining the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. The antiproliferative effects of Lophira alata were assessed using the MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways such as Akt, mTOR, PARP and caspases. The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell viability and cell proliferation. In addition, LAM attenuated phorbol 12-myristate 13-acetate (PMA)-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha abrogated LAM-mediated downregulation of Akt. Our data also revealed that treatment with LAM induced both PARP and caspase cleavage. The HPLC fingerprint of the fraction indicates the presence of the flavonoids luteolin and rutin, which are known to inhibit the proliferation of glioblastoma cells.
Creative Commons License
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Lophira Alata Suppresses Glioblastoma Cell Growth via Inhibition of Protein Kinase C-α
The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in malignant brain tumor cells. This study was aimed at examining the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. The antiproliferative effects of Lophira alata were assessed using the MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways such as Akt, mTOR, PARP and caspases. The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell viability and cell proliferation. In addition, LAM attenuated phorbol 12-myristate 13-acetate (PMA)-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha abrogated LAM-mediated downregulation of Akt. Our data also revealed that treatment with LAM induced both PARP and caspase cleavage. The HPLC fingerprint of the fraction indicates the presence of the flavonoids luteolin and rutin, which are known to inhibit the proliferation of glioblastoma cells.
