DOI QR코드

DOI QR Code

Effects of Smilax China L. on the Growth of Skin Cancer Cells

토복령(土茯笭)이 피부암 세포의 성장에 미치는 영향

  • Si-Yeol Song (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Dongshin University) ;
  • Min-Yeong Jung (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Dongshin University) ;
  • Jeong-Hwa Choi (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Dongshin University) ;
  • Soo-Yeon Park (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Dongshin University)
  • 송시열 (동신대학교 한의과대학 한방안이비인후피부과학교실) ;
  • 정민영 (동신대학교 한의과대학 한방안이비인후피부과학교실) ;
  • 최정화 (동신대학교 한의과대학 한방안이비인후피부과학교실) ;
  • 박수연 (동신대학교 한의과대학 한방안이비인후피부과학교실)
  • Received : 2024.01.05
  • Accepted : 2024.01.26
  • Published : 2024.02.25

Abstract

Objectives : We aimed to study the effect of Smilax China L.(SCL), which has anti-inflammatory, antioxidant, and anticancer effects, on the growth of skin cancer cells. Methods : HaCaT cells, a normal human cell line, and skin cancer cells including A431, SK-MEL-5 and SK-MEL-28 cells were treated with Smilax China L. ethanol extract(SCL-EtOH) at concentrations of 5, 10, 20 and 40㎍/㎖. Meanwhile, JB6 Cl41, a normal mouse epithelial cell line, was treated with epidermal growth factor(EGF) and phorbol 12-myristate 13-acetate(TPA), an inflammatory factor, to induce cell transformation and treated with SCL-EtOH. In addition, we treated SK-MEL-5 and SK-MEL-28 cells with SCL-EtOH at various concentrations and checked the effect on the cell cycle. Results : As a result, it showed no toxicity to HaCaT cells up to the highest concentration of 40㎍/㎖, and significant cell growth inhibition to A431, SK-MEL-5 and SK-MEL-28 cells in a time- and concentration-dependent manner. In addition, as a result of checking the shape of skin cancer cells according to SCL-EtOH treatment, it was observed that as the concentration increased, the number of normally attached and growing cells decreased and the shape of the cells changed. Colony formation was significantly reduced in a concentration-dependent manner in JB6 Cl41 cells treated with EGF or TPA. Flow cytometry analysis with propidium iodide(PI) staining showed that SCL-EtOH induced the G2/M phase arrest. We further confirmed the decrease in Cyclin B1 expression and increase in p27 expression associated with the G2/M phase of the cell cycle through western blot analysis. Flow cytometry analysis confirmed that SCL-EtOH induced cell apoptosis. Furthermore, through Western blot analysis, it was observed that the expression of cleaved-caspase-7, which is related to apoptosis, increased. Finally, it was confirmed that the expression of COX-2, an inflammatory marker protein, decreased in a concentration-dependent manner with SCL-EtOH. Conclusions : Through the above results, we have established a basis for applying SCL to the treatment of skin cancer.

Keywords

References

  1. Korean Dermatological Association Textbook Compilation Committee. Text book of Dermatology. Seoul:McGraw-Hill. 2020:613-45.
  2. Department of Dermatology, College of Medicine, Seoul National University. Dermatology for Medical Students. Seoul:Korea Medicine. 2023:280-95.
  3. Kim HN. Dermatology in an easy-to-understand way. Seoul:Medical Seowon. 2017: 276-90.
  4. Paul K. Buxton. Dermatology understood at once. Seoul:Korean Medicine. 2012:179-88.
  5. Apalla Z, Nashan D, Weller RB, Castellsague X. Skin Cancer: Epidemiology,Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches. Dermatol Ther(Heidelb). 2017;7(Suppl 1):5-19.
  6. Lopez AT, Carvajal RD, Geskin L. Secondary Prevention Strategies for Nonmelanoma Skin Cancer. Oncology (Williston Park). 2018;32(4):195-200.
  7. Paulson KG, Lahman MC, Chapuis AG, Brownell I. Immunotherapy for skin cancer. Int Immunol. 2019;31(7):465-75.
  8. Kim CM, Shin MK, Ahn DG, Lee GS. A dictionary of Chinese medicine. Seoul:Jeong Dam. 2006:1516-9.
  9. Traditional Herbology Common Textbook Compilation Committee. Traditional Herbology. Seoul:Yeong Lim's Publisher. 2020:265-7.
  10. Xu M, Xue H, Qiao G, Liao M, Kong L, Zhang Q, et al. Regulating the Imbalance of Gut Microbiota by Smilax china L. Polyphenols to Alleviate Dextran Sulfate Sodium-induced Inflammatory Bowel Diseases. Am J Chin Med. 2022;50(2):553-68.
  11. Feng H, He Y, La L, Hou C, Song L, Yang Q, et al. The flavonoid-enriched extract from the root of Smilax china L. inhibits inflammatory responses via the TLR-4-mediated signaling pathway. J Ethnopharmacol. 2020;256:112785.
  12. Zhang Y, Pan X, Ran S, Wang K. Purification, structural elucidation and anti-inflammatory activity in vitro of polysaccharides from Smilax china L. Int J Biol Macromol. 2019;139:233-43.
  13. Jang TW, Oh CG, Park JH. Antioxidant activity and protective effects on oxidative DNA damage of Smilax china root. Journal of Applied Biological Chemistry. 2018;61(2);109-17.
  14. Kang YH, Kim KK, Kim DJ, Choe M. Antiobesity effects of the water-soluble fraction of the ethanol extract of Smilax china L. leaf in 3T3-L1 adipocytes. Nutr Res Pract. 2015;9(6):606-12.
  15. Park JA, Jin KS, Kwon HJ, Kim BW. The Anti-Obesity Effect of Smilax china Extract. Korean Journal of Microbiology and Biotechnology. 2014;42(4):354-60.
  16. Wang C, Zhou Q, Wu ST. Scopolin obtained from Smilax china L. against hepatocellular carcinoma by inhibiting glycolysis: A network pharmacology and experimental study. J Ethnopharmacol. 2022;296:115469.
  17. Hu LL, Chen DS, Wang YY, Qin Y, Huang P, Yu LX, et al. Smilax china L. rhizome extract inhibits nuclear factor-κB and induces apoptosis in ovarian cancer cells. Chin J Integr Med. 2015;21(12):907-15.
  18. Nho KJ, Chun JM, Kim HK. Anti-metastatic effect of Smilax china L. extract on MDA-MB-231 cells. Mol Med Rep. 2015;11(1):499-502.
  19. Yu HJ, Shin JA, Lee SO, Kwon KH, Cho SD. Extracellular signal‑regulated kinase inhibition is required for methanol extract of Smilax china L.‑induced apoptosis through death receptor 5 in human oral mucoepidermoid carcinoma cells. Mol Med Rep. 2014;9(2):663-8.
  20. Fu X, Zhao R, Yoon G, Shim JH, Choi BY, Yin F, et al. 3-Deoxysappanchalcone Inhibits Skin Cancer Proliferation by Regulating T-Lymphokine-Activated Killer Cell-Originated Protein Kinase in vitro and in vivo. Front Cell Dev Biol. 2021;9:638174.
  21. Hwang SY, Chae JI, Kwak AW, Lee MH, Shim JH. Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways. Int J Mol Sci. 2020;21(18):6869.
  22. Korean Statistical Information Service [Internet]. Ministry of Health and Welfare;Cancer statistics in Korea;Number of cancer patients, relative frequency, crude rate, age-adjusted incidence by cancer site and sex. 2020[cited 2023 Nov 30]. Available from: URL:https://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_117N_A00025&conn_path=I2
  23. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
  24. Arnold M, Singh D, Laversanne M, Vignat J, Vaccarella S, Meheus F. Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040. JAMA Dermatol. 2022;158(5):495-503.
  25. Cunha C, Marinheiro D, Ferreira BJML, Oliveira H, Daniel-da-Silva AL. Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy. Mol ecules. 2023;28(12):4776.
  26. Malyarenko OS, Usoltseva RV, Silchenko AS, Zueva AO, Ermakova SP. The Combined Metabolically Oriented Effect of Fucoidan from the Brown Alga Saccharina cichorioides and Its Carboxymethylated Derivative with 2-Deoxy-D-Glucose on Human Melanoma Cells. Int J Mol Sci. 2023;24(15):12050.
  27. Yu PY. Inhibitory Effects of Chrysanthemum indicum L. on Skin Inflammation and Skin Cancer. Naju: The Graduate School of Dongsh in University. 2023:48-54.
  28. Park HJ, Go YS. A literature studies on the cause, symptom and treatment of the Bun-Hwa-Chang(翻花瘡). The journal of oriental medical surgery, Ophthalmology&Otolaryngology. 1997;10(1):136-7.
  29. Herbal Pharmacology Compilation Committee. Herbal Pharmacology. 5th ed. Seoul:Shinil Books. 2023:246-7.
  30. Lee CJ, Lee MH, Cho YY. Fibroblast and Epidermal Growth Factors Utilize Different Signaling Pathways to Induce Anchorage-independent Cell Transformation in JB6 Cl41 Mouse Skin Epidermal Cells. J Cancer Prev. 2014;19(3):199-208.
  31. Kinoshita M, Yamada A, Sasa K, Ikezaki K, Shirota T, Kamijo R. Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors. Sci Rep. 2021;11(1):20360.
  32. Oi N, Yamamoto H, Langfald A, Bai R, Lee MH, Bode AM, et al. LTA4H regulates cell cycle and skin carcinogenesis. Carcinogenesis. 2017;38(7):728-37.
  33. Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131-49.
  34. Ghafouri-Fard, S, Khoshbakht T, Hussen BM, Dong P, Gassler N, et al. A review on the role of cyclin dependent kinases in cancers. Cancer Cell International. 2022;22(1):325.
  35. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2007;121(11):2373-80.
  36. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073-81.