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Published on: January 22, 2019
Blackberry extracts inhibit activating protein 1 activation and cell transformation by perturbing the mitogenic
Rentian Feng1, Linda L Bowman, Yongju Lu
1Pathology and Physiology Research Branch, Helath Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Abstract:
Blackberries are natural rich sources of bioflavonoids and phenolic compounds that are commonly known as potential chemopreventive agents. Here, we investigated the effects of fresh blackberry extracts on proliferation of cancer cells and neoplastic transformation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as well as the underlying mechanisms of signal transduction pathways. Using electron spin resonance, we found that blackberry extract is an effective scavenger of free radicals, including hydroxyl and superoxide radicals. Blackberry extract inhibited the proliferation of a human lung cancer cell line, A549. Pretreatment of A549 cells with blackberry extract resulted in an inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation induced by ultraviolet B (UVB) irradiation. Blackberry extract decreased TPA-induced neoplastic transformation of JB6 P+ cells. Pretreatment of JB6 cells with blackberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 transactivation. Furthermore, blackberry extract also blocked UVB- or TPA-induced phosphorylation of ERKs and JNKs, but not p38 kinase. Overall, these results indicated that an extract from fresh blackberry may inhibit tumor promoter-induced carcinogenesis and associated cell signaling, and suggest that the chemopreventive effects of fresh blackberry may be through its antioxidant properties by blocking reactive oxygen species-mediated AP-1 and mitogen-activated protein kinase activation.
Insights
Blackberry extract, rich in antioxidants, effectively inhibits cancer cell proliferation and neoplastic transformation. It works by scavenging free radicals and blocking key signaling pathways involved in carcinogenesis.
Area of Science:
- Phytochemistry
- Cancer Biology
- Molecular Signaling
Background:
- Blackberries are rich in bioflavonoids and phenolic compounds with potential chemopreventive properties.
- Cancer development involves cell proliferation, neoplastic transformation, and complex signaling pathways.
- Understanding the mechanisms of natural compounds is crucial for developing cancer prevention strategies.
Purpose of the Study:
- To investigate the effects of fresh blackberry extracts on cancer cell proliferation and neoplastic transformation.
- To elucidate the underlying signal transduction mechanisms affected by blackberry extract.
- To evaluate the antioxidant capacity and free radical scavenging activity of blackberry extract.
Main Methods:
- Electron spin resonance (ESR) for free radical scavenging assessment.
- In vitro assays using human lung cancer cell line (A549) and JB6 P+ cells.
- Measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, AP-1 transactivation, and MAPK phosphorylation (ERK, JNK, p38).
Main Results:
- Blackberry extract demonstrated significant free radical scavenging activity.
- Extract inhibited A549 cell proliferation and UVB-induced 8-OHdG formation.
- Extract suppressed TPA-induced neoplastic transformation in JB6 cells.
- Blackberry extract blocked UVB- and TPA-induced AP-1 transactivation and phosphorylation of ERK and JNK pathways.
Conclusions:
- Fresh blackberry extract exhibits chemopreventive potential against tumor promoter-induced carcinogenesis.
- Antioxidant properties of blackberry extract contribute to its effects by inhibiting reactive oxygen species (ROS).
- The extract modulates key signaling pathways, including AP-1 and MAPK, suggesting a role in cancer prevention.
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