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Harnessing the Power of Kiwifruit for Radiosensitization of Melanoma
Leon Kou1,2, Ziwen Zhu3, Emerson Fajardo3
1HCA Healthcare/USF Morsani College of Medicine GME/St. Petersburg General Hospital, St. Petersburg, FL, U.S.A.
Background:
Melanoma is the deadliest variant of skin cancer and its incidence continues to increase. There are limited treatment options for advanced and metastatic cases of melanoma, despite advances in immunotherapy and chemotherapy. Melanoma is notorious as a radioresistant tumor. Previous studies found that phytochemicals, such as resveratrol and those found in green tea and blueberry, can sensitize various cancer cells, including melanoma, to radiotherapy. Our previous study also revealed that kiwifruit extract (KE) has antitumor activity to melanoma cells. This study was designed to expand upon our previous investigation and determine KE's potential as a radiosensitizer on CRL-11147 melanoma cancer cells and elucidate the possible mechanisms behind its potential.
Materials And Methods:
Proliferation and apoptosis of CRL-11147 melanoma cells under radiation therapy (RT) plus KE versus RT alone were investigated using Proliferative cell nuclear antigen (PCNA) staining, quick cell proliferation assay, clonogenic assay, and caspase-3 activity assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were then used to investigate the mechanisms behind the observed results.
Results:
The percentage of CRL-11147 colonies, PCNA staining intensity, and the optic density value of CRL-11147 cells decreased with RT/KE vs. RT alone. Relative caspase-3 activity was increased with RT/KE vs. RT alone. Increased expression of the anti-proliferative molecule p27 and pro-apoptotic molecule TRAILR1 correlated with the anti-tumor effect seen in the RT/KE group versus the RT alone group.
Conclusion:
KE augments radiosensitivity of CRL-11147 by up-regulating both p27 and TRAILR1 to inhibit proliferation and increase apoptosis, respectively.
Insights
Kiwifruit extract (KE) enhances melanoma cancer cell radiosensitivity by increasing apoptosis and inhibiting proliferation. This extract shows promise in improving radiation therapy (RT) outcomes for melanoma.
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Melanoma is an aggressive skin cancer with limited treatment options for advanced stages.
- Melanoma exhibits significant radioresistance, posing a challenge for radiotherapy.
- Phytochemicals show potential in sensitizing cancer cells to radiation, with prior research indicating kiwifruit extract (KE) possesses antitumor properties against melanoma.
Purpose of the Study:
- To evaluate the radiosensitizing potential of kiwifruit extract (KE) on CRL-11147 melanoma cells.
- To investigate the underlying mechanisms by which KE might enhance radiosensitivity.
Main Methods:
- CRL-11147 melanoma cells were treated with radiation therapy (RT) alone or in combination with KE.
- Cell proliferation was assessed using Proliferative Cell Nuclear Antigen (PCNA) staining and clonogenic assays.
- Apoptosis was measured via caspase-3 activity assays.
- Gene and protein expression of key regulators were analyzed using RT-PCR and immunohistochemistry (IHC).
Main Results:
- Combined treatment of RT and KE significantly reduced melanoma cell proliferation and colony formation compared to RT alone.
- KE treatment in conjunction with RT led to increased caspase-3 activity, indicating enhanced apoptosis.
- The expression of p27 (anti-proliferative) and TRAILR1 (pro-apoptotic) was upregulated in cells treated with RT/KE.
Conclusions:
- Kiwifruit extract (KE) effectively augments the radiosensitivity of CRL-11147 melanoma cells.
- KE enhances radiosensitivity by upregulating p27, thereby inhibiting proliferation, and by upregulating TRAILR1, thereby promoting apoptosis.
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