Abstract
Purpose : To investigate the anti-cancer activities of C5 extract (C5E), a new herbal preparation from Korea, on B16F10 cells. Methods : The anti-proliferative effects of C5E were assessed by culturing B16F10 cells in the presence or absence of C5E. Cell cycle progression was analyzed by PI staining using flow cytometry. The quantities of apoptosis-inducing proteins were measured by Western blot. Results : C5E inhibited the proliferation of B16F10 cells but not human keratinocytes. C5E induced S phase arrest by interfering with cell regulatory factors such as cyclins B1, D1, D3, and E, and cyclindependent kinase 2, in B16F10 cells. Furthermore, immunoblot analysis confirmed that treatment with C5E induced apoptosis and cleaved caspase-3, poly (ADP-ribose) polymerase, via extrinsic pathway, whereas Bcl-2 expression was down-regulated. In addition, the suppression of cell proliferation by C5E is through down-regulation of p-Akt, up-regulation of phosphatase and tensin homolog protein expression via phosphoinositol 3 kinase survival signaling pathways in B16F10 cells. The combined cytotoxic effects of C5E and vinblastine generated 10 % increase in activity in contrast to the sum of the inhibitory effects of the individual agents. Conclusion : C5E shows promising anti-cancer activity and can be a useful adjuvant with vinblastine in combination therapeutic treatment of skin cancer. Keywords : Melanoma, Apoptosis, Anti-cancer, p53, Vinblastine, Cell cycle arrest, Caspase
Highlights
Metastasis, invasion, angiogenesis, and uncontrolled growth are characteristics of cancer
We investigated the inhibitory effect of C5 extract (C5E) on the proliferation of B16F10 cells, its ability to induce apoptosis via both the extrinsic and intrinsic pathways, and its effect on phosphoinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) survival signaling pathways
In order to understand the cause of cytotoxic effects induced by C5E in B16F10 melanoma, we investigated apoptotic signaling using western blot analyses and immunohistochemistry
Summary
Metastasis, invasion, angiogenesis, and uncontrolled growth are characteristics of cancer. Cancer is a fatal disease that requires a multipronged therapeutic approach. Chinese herbal medicines exert multiple effects to inhibit metastasis, angiogenesis, and tumor growth [1]. Herbal medicines are generally abundant with low cost, and relatively non-toxic, and plant extracts are thought to be therapeutically superior to anti-cancer drugs in some cases [2,3]. Apoptosis is an important mode of programmed cell death, which is very different from necrosis [4]. Apoptotic cells undergo characteristic changes such as chromatin condensation, nuclear fragmentation, and blebbing [5]
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