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Kolaviron-Induced Inhibition of Lung Adencarcinoma (H1299) Cell Growth and Survival via PKA/PI3K Pathway
Başlık:
Kolaviron-Induced Inhibition of Lung Adencarcinoma (H1299) Cell Growth and Survival via PKA/PI3K Pathway
Yazar:
Blake, Courtney Renee, author.
ISBN:
9780438014008
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (90 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Momoh Yakubu Committee members: Audrey Player; Lalita Sen; Zivar Yousefipour.
Özet:
Kolaviron (KV), a natural bioflavonoid obtained from the seeds of Garcinia kola, has been noted for its diverse pharmacological actions such as its antioxidative, antiproliferative, and anti-inflammatory properties. We tested KV for phytochemical content considering that phytochemicals have been shown to hold anticancer properties. The sodium hydroxide and ferric chloride test both confirmed that KV contained two major phytochemicals: flavonoids and tannins, respectively. We also evaluated the antiproliferative and cytotoxic effects of KV on H1299 lung cancer cell line. H1299 cell line was cultured in modified medium fortified with 10% FBS and 1% Antibiotic/ antimycotic using 96 well plates. The effects of KV (25-1000 mug/mL) on H1299 proliferation were determined 24 hrs. or 48 hrs. (cytotoxic/apoptosis) after plating using MTT assay. MTT assay indicated that KV dose-and time -dependently inhibited H1299 cell proliferation as well as caused cell death in the cytotoxic studies. These effects were significantly different from the control. The cytotoxic effects of KV were only partially reversed at 24 and 48 hrs. following treatment with cell division/ cell growth inhibitor, 2',5'-dideoxyadenosine (10 muL of cAMPi (10 muM)) and protein kinase C inhibitor, Calphostin C(10muL of CC (10muM) ). The results showed that while 2', 5'-dideoxyadenosine(cAMPi) moderated cell growth and division in H1299 cells, KV further induced cytotoxicity in H1299 cells treated with 2', 5' dideoyxyadenosine. Protein kinase C inhibitor Calphostin C (CC) attenuated cell growth and cell division in H1299 cells; however, Kolaviron inhibited cell growth of H1299 cells independently of PKC activity. With respect to the mechanism by which KV exerts its antiproliferative and cytotoxic effects, we investigated the effects of Kolaviron in the presence and absence of small molecular inhibitors on protein expression for survival/ death pathways, specifically PI3K-Akt and the Caspases. H1299 cells were treated with 25 mug/mL in the presence or absence of .6 muM of Wortmannin (WT), a PI3K inhibitor. Using western blotting, we found that KV mediates Akt activity and exerts inhibition through ERK signaling pathway. With respect to cell survival we found that Bcl-xL is not a mechanism employed by KV to inhibit cell proliferation. Also, KV potentially executes apoptosis via extrinsic pathway.
These observations indicated that KV mediates its cytotoxic effects via inhibition of pro-survival and pro-apoptotic signals regulated by cAMP modulated downstream effectors through PKA/PI3K pathways. These results suggest that KV has therapeutic potential against lung cancer and the mechanisms of actions need further investigation.
Notlar:
School code: 0441
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(682124.1) | 682124-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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