Skip to main content

Advertisement

SpringerLink
Log in

Potential use of kiwifruit extract for treatment of melanoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Skin cancers are the most common cancers in the world and among the different types of skin cancers, melanoma is the deadliest and incidence is rising. Previous studies have shown promising in vitro and human evidence of kiwifruit exhibiting anti-cancer effects. This study was designed to investigate if kiwifruit extract (KE) has any effect on CRL-11147 melanoma cancer cells and to investigate the possible mechanisms behind the results. The effects of KE on CRL-11147 melanoma cell survival, proliferation, and apoptosis was investigated using clonogenic survival assay, cell proliferation, and caspase-3 activity kits. Potential anti-tumor molecular mechanisms were elucidated using RT-PCR and IHC. Addition of KE decreased CRL-11147 cell colonies percentages indicated by a decreased optical density value of cancer cells when compared to control. Furthermore, treatment with KE increased relative caspase-3 activity in cancer cells, which indicated increased apoptosis of cancer cells. The anti-proliferative effect of KE on cancer cells corresponded with decreased expression of the pro-proliferative molecule Cyclin E and CDK4, while increased expression of the pro-apoptotic molecule TRAILR1 corresponded with the pro-apoptotic effect. KE decreases CRL-11147 melanoma cell growth via downregulation of Cyclin E and CDK4 and upregulation in TRAILR1. Our study suggests a potential use for KE in treatment of melanoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.

    Article  Google Scholar 

  2. Rainov NG, Burkert W. Miliary brain metastases from malignant melanoma. Zentralbl Neurochir. 1996;57(1):20–4.

    CAS  PubMed  Google Scholar 

  3. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865–72. https://doi.org/10.1200/JCO.2004.12.149.

    Article  PubMed  Google Scholar 

  4. Chiarion-Sileni V, Guida M, Ridolfi L, Romanini A, Del Bianco P, Pigozzo J, et al. Central nervous system failure in melanoma patients: results of a randomised, multicentre phase 3 study of temozolomide-and dacarbazine-based regimens. Br J Cancer. 2011;104(12):1816–21.

    Article  CAS  Google Scholar 

  5. Sul J, Posner JB. Brain metastases: epidemiology and pathophysiology. Brain metastases. New York: Springer; 2007. p. 1–21.

    Book  Google Scholar 

  6. Trucco LD, Mundra PA, Hogan K, Garcia-Martinez P, Viros A, Mandal AK, et al. Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma. Nat Med. 2019;25(2):221–4.

    Article  CAS  Google Scholar 

  7. Cohen JV, Tawbi H, Margolin KA, Amravadi R, Bosenberg M, Brastianos PK, et al. Melanoma central nervous system metastases: current approaches, challenges, and opportunities. Pigment Cell Melanoma Res. 2016;29(6):627–42. https://doi.org/10.1111/pcmr.12538.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Livingstone A, Agarwal A, Stockler MR, Menzies AM, Howard K, Morton RL. Preferences for immunotherapy in melanoma: a systematic review. Ann Surg Oncol. 2020;27(2):571–84. https://doi.org/10.1245/s10434-019-07963-y.

    Article  PubMed  Google Scholar 

  9. Rubio-Rodriguez D, De Diego BS, Perez M, Rubio-Terres C. Cost-effectiveness of drug treatments for advanced melanoma: a systematic literature review. Pharmacoeconomics. 2017;35(9):879–93. https://doi.org/10.1007/s40273-017-0517-1.

    Article  PubMed  Google Scholar 

  10. Lippi G, Mattiuzzi C. Kiwifruit and cancer: an overview of biological evidence. Nutr Cancer. 2020;72(4):547–53. https://doi.org/10.1080/01635581.2019.1650190.

    Article  CAS  PubMed  Google Scholar 

  11. Johnson GE, Ivanov VN, Hei TK. Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis. 2008;13(6):790.

    Article  CAS  Google Scholar 

  12. Wu F, Cui L. Resveratrol suppresses melanoma by inhibiting NF-kappaB/miR-221 and inducing TFG expression. Arch Dermatol Res. 2017;309(10):823–31. https://doi.org/10.1007/s00403-017-1784-6.

    Article  CAS  PubMed  Google Scholar 

  13. Fang Y, Bradley MJ, Cook KM, Herrick EJ, Nicholl MB. A potential role for resveratrol as a radiation sensitizer for melanoma treatment. J Surg Res. 2013;183(2):645–53.

    Article  CAS  Google Scholar 

  14. Fang Y, Chen X, Bai Q, Qin C, Mohamud AO, Zhu Z, et al. IL-9 inhibits HTB-72 melanoma cell growth through upregulation of p21 and TRAIL. J Surg Oncol. 2015;111(8):969–74.

    Article  CAS  Google Scholar 

  15. Fang Y, DeMarco VG, Nicholl MB. Resveratrol enhances radiation sensitivity in prostate cancer by inhibiting cell proliferation and promoting cell senescence and apoptosis. Cancer Sci. 2012;103(6):1090–8. https://doi.org/10.1111/j.1349-7006.2012.02272.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhu Z, Davidson KT, Brittingham A, Wakefield MR, Bai Q, Xiao H, et al. Trichomonas vaginalis: a possible foe to prostate cancer. Med Oncol. 2016;33(10):115. https://doi.org/10.1007/s12032-016-0832-y.

    Article  PubMed  Google Scholar 

  17. Johnson DG, Walker CL. Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol. 1999;39:295–312. https://doi.org/10.1146/annurev.pharmtox.39.1.295.

    Article  CAS  PubMed  Google Scholar 

  18. Sherr CJ, Roberts JM. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 2004;18(22):2699–711.

    Article  CAS  Google Scholar 

  19. Zhang D, Li X, Chen C, Li Y, Zhao L, Jing Y, et al. Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration. PLoS ONE. 2012;7(7):e41478. https://doi.org/10.1371/journal.pone.0041478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhu Z, Zhang D, Lee H, Menon AA, Wu J, Hu K, et al. Macrophage-derived apoptotic bodies promote the proliferation of the recipient cells via shuttling microRNA-221/222. J Leukoc Biol. 2017;101(6):1349–59. https://doi.org/10.1189/jlb.3A1116-483R.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Donnellan R, Chetty R. Cyclin E in human cancers. FASEB J. 1999;13(8):773–80. https://doi.org/10.1096/fasebj.13.8.773.

    Article  CAS  PubMed  Google Scholar 

  22. Kollmann K, Briand C, Bellutti F, Schicher N, Blunder S, Zojer M, et al. The interplay of CDK4 and CDK6 in melanoma. Oncotarget. 2019;10(14):1346–59. https://doi.org/10.18632/oncotarget.26515.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zhao H, Zheng B. Dual targeting of autophagy and MEK in KRAS mutant cancer. Trends Cancer. 2019;5(6):327–9. https://doi.org/10.1016/j.trecan.2019.04.003.

    Article  CAS  PubMed  Google Scholar 

  24. Bartkova J, Lukas J, Guldberg P, Alsner J, Kirkin AF, Zeuthen J, et al. The p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis. Can Res. 1996;56(23):5475–83.

    CAS  Google Scholar 

  25. Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, et al. Germline p16 mutations in familial melanoma. Nat Genet. 1994;8(1):15–21. https://doi.org/10.1038/ng0994-15.

    Article  CAS  PubMed  Google Scholar 

  26. Sharpless NE, Chin L. The INK4a/ARF locus and melanoma. Oncogene. 2003;22(20):3092–8.

    Article  CAS  Google Scholar 

  27. Wajant H. TRAIL-and TNF-induced signaling complexes—so similar yet so different. EMBO J. 2017;36(9):1117–9.

    Article  CAS  Google Scholar 

  28. Gerspach J, Pfizenmaier K, Wajant H. Therapeutic targeting of CD95 and the TRAIL death receptors. Recent Pat Anticancer Drug Discov. 2011;6(3):294–310. https://doi.org/10.2174/157489211796957739.

    Article  CAS  PubMed  Google Scholar 

  29. Oka K, Suzuki Y, Nakano T. Expression of p27 and p53 in cervical squamous cell carcinoma patients treated with radiotherapy alone: radiotherapeutic effect and prognosis. Cancer. 2000;88(12):2766–73. https://doi.org/10.1002/1097-0142(20000615)88:12%3c2766::aid-cncr15%3e3.0.co;2-g.

    Article  CAS  PubMed  Google Scholar 

  30. McKean MA, Amaria RN. Multidisciplinary treatment strategies in high-risk resectable melanoma: role of adjuvant and neoadjuvant therapy. Cancer Treat Rev. 2018;70:144–53. https://doi.org/10.1016/j.ctrv.2018.08.011.

    Article  CAS  PubMed  Google Scholar 

  31. Kim MM, Parmar H, Cao Y, Pramanik P, Schipper M, Hayman J, et al. Whole brain radiotherapy and RRx-001: two partial responses in radioresistant melanoma brain metastases from a phase I/II clinical trial: a TITE-CRM phase I/II clinical trial. Transl Oncol. 2016;9(2):108–13. https://doi.org/10.1016/j.tranon.2015.12.003.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Singh M, Alavi A, Wong R, Akita S. Radiodermatitis: a review of our current understanding. Am J Clin Dermatol. 2016;17(3):277–92.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from Des Moines University for Yujiang Fang.

Author information

Authors and Affiliations

  1. Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA, 50312, USA

    Leon Kou, Marco Lequio & Yujiang Fang

  2. Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA

    Ziwen Zhu, Chase Redington, Qian Bai, Mark Wakefield, Marco Lequio & Yujiang Fang

Authors
  1. Leon Kou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ziwen Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chase Redington
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark Wakefield
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco Lequio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yujiang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yujiang Fang.

Ethics declarations

Conflict of interest

The authors have no disclosures.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kou, L., Zhu, Z., Redington, C. et al. Potential use of kiwifruit extract for treatment of melanoma. Med Oncol 38, 25 (2021). https://doi.org/10.1007/s12032-021-01465-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-021-01465-2

Keywords

Search

Navigation