Effects of Shark Cartilage on Heterotransplanted Oral Squamous Cell Carcinoma Induced in Nude Mice
Journal of Dental School, Shahid Beheshti University of Medical Sciences,
Vol. 41 No. 3 (2023),
13 March 2024
,
Page 115-122
https://doi.org/10.22037/jds.v41i3.43856
Abstract
Objectives The use of shark cartilage as a supplementary treatment has a long yet unresolved history in the realm of complementary-alternative medicine. This study aimed to investigate the impact of concentrated and purified extracts from Persian Gulf shark cartilage (PGSC) on oral cavity squamous cell carcinoma (SCC) (specifically, the KB cell line) induced in an animal model.
Methods Ectopic tumors of oral cavity SCC were induced in eight nude mice through the heterotransplantation of the KB cell line. Once the tumor volume reached 100 mm3, the mice were randomly divided into two groups: treatment and control. The treatment group received shark cartilage at a dosage of 50 mg/kg body weight, while the control group received a phosphate buffer. The drug was administered daily for four days via the intraperitoneal route. Following this, the drug administration was halted for a period of five days before resuming (as per the NCI protocol). After 54 days, the animals were sacrificed, and their tumors were sent for immunohistochemical evaluation using Ki-67 and CD34 markers.
Results The findings revealed a significant reduction in intratumoral blood vessels in the treatment group compared to the control group (P-value = 0.001). While there was a decrease in both the size of the tumor and the proliferation of tumor cells, this reduction was not statistically significant. The average proliferation index was 13.33% for the treatment group and 33.33% for the control group.
Conclusion Significant decrease in intra-tumoral vascularity can control tumor spreading and metastasis, potentially playing an important role in cancer management of oral cavity SCC.
- Squamous Cell Carcinoma
- Shark Cartilage
- CD34
- ki-67
- Oral Cancer
How to Cite
References
Bai S, Yan YB, Chen W, Zhang P, Zhang TM, Tian YY, et al. Bioinformatic analysis reveals an immune/inflammatory-related risk signature for oral cavity squamous cell carcinoma. J Oncol. 2019:2019:3865279.
Yang S, Su JZ, Gao Y, Yu GY. Clinicopathological study of involvement of the submandibular gland in oral squamous cell carcinoma. Br J Oral Maxillofac Surg. 2020;58(2):203-7.
Fonseca RJ. Oral and Maxillofacial Surgery-E-Book: Volume 2 2nd Edition.
Li CC, Shen Z, Bavarian R, Yang F, Bhattacharya A. Oral cancer: genetics and the role of precision medicine. Dent Clin North Am. 2018;62(1):29-46.
Quinlan-Davidson SR, Mohamed AS, Myers JN, Gunn GB, Johnson FM, Skinner H, et al. Outcomes of oral cavity cancer patients treated with surgery followed by postoperative intensity modulated radiation therapy. Oral Oncol. 2017:72:90-7.
Subramaniam SS, Paterson C, McCaul JA. Immunotherapy in the management of squamous cell carcinoma of the head and neck. Br J Oral Maxillofac Surg. 2019;57(10):957-66.
Bell RB, Leidner R, Feng Z, Crittenden MR, Gough MJ, Fox BA. Developing an immunotherapy strategy for the effective treatment of oral, head and neck squamous cell carcinoma. J Oral Maxillofac Surg. 2015;73(12 Suppl):S107-15.
Meulemans J, Delaere P, Vander Poorten V. Photodynamic therapy in head and neck cancer: indications, outcomes, and future prospects. Curr Opin Otolaryngol Head Neck Surg. 2019;27(2):136-41.
Chu PL, Shihabuddeen WA, Low KP, Poon DJ, Ramaswamy B, Liang ZG, et al. Vandetanib sensitizes head and neck squamous cell carcinoma to photodynamic therapy through modulation of EGFR-dependent DNA repair and the tumour microenvironment. Photodiagnosis Photodyn Ther. 2019:27:367-74.
Farmer ZL, Kim ES, Carrizosa DR. Gene therapy in head and neck cancer. Oral Maxillofac Surg Clin North Am. 2019;31(1):117-24.
Luo Q, Asher GN. Complementary and alternative medicine use at a comprehensive cancer center. Integr Cancer Ther. 2017;16(1):104-9.
Nilsson J, Källman M, Östlund U, Holgersson G, Bergqvist M, Bergström S. The use of complementary and alternative medicine in Scandinavia. Anticancer Res. 2016;36(7):3243-51.
Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science. 1983;221(4616):1185-7.
Dupont E, Brazeau P, Juneau C, Maes DH, Marenus K, inventors; Les Laboratories Aeterna Inc, assignee. Methods of using extracts of shark cartilage. United States patent US. 2000; p:6,028,118.
Patra D, Sandell LJ. Antiangiogenic and anticancer molecules in cartilage. Expert Rev Mol Med. 2012:14:e10.
Shahrokhi S, Zuhair MH, Mohagheghi MA, Ghazanfari T, Ebtekar M. Shark cartilage modulates immune responses in stage III breast cancer patients. Int J Hematol Oncol Stem Cell Res. 2009:21-8.
Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 1989;24(3):148-54.
Hassan ZM, Feyzi R, Sheikhian A, Bargahi A, Mostafaie A, Mansouri K, et al. Low molecular weight fraction of shark cartilage can modulate immune responses and abolish angiogenesis. Int Immunopharmacol. 2005;5(6):961-70.
Safari E, Hassan ZM, Moazzeni SM. Shark cartilage 14 kDa protein as a dendritic cells activator. IImmunopharmacol Immunotoxicol. 2015;37(2):165-70.
Folkman J. Toward an understanding of angiogenesis: search and discovery. Perspect Biol Med. 1985;29(1):10-36.
Gonzalez RP, Leyva A, Moraes MO. Shark cartilage as source of antiangiogenic compounds: from basic to clinical research. Biol Pharm Bull. 2001;24(10):1097-101.
Krichen F, Bougatef H, Sayari N, Capitani F, Amor IB, Koubaa I, et al. Isolation, purification and structural characterestics of chondroitin sulfate from smooth hound cartilage: In vitro anticoagulant and antiproliferative properties. Carbohydr Polym. 2018:197:451-9.
Dupont E, Savard PE, Jourdain C, Juneau C, Thibodeau A, Ross N, et al. Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis. J Cutan Med Surg. 1998;2(3):146-52.
Cernak M, Nogova L. Current antiangiogenic agents in oncology and ophthalmology. Neoplasma. 2016;63(1):10-7.
Chuan-Ying Y, Lei Z. Effects of shark cartilage polysaccharides on the secretion of IL-6 and IL-12 in rheumatoid arthritis. Pharm Biol. 2012;50(12):1567-72.
Mao JW, He XM, Tang HY, Wang YD. Protective role of metalloproteinase inhibitor (AE-941) on ulcerative colitis in rats. World J Gastroenterol. 2012;18(47):7063-9.
Dupont É, Falardeau P, Mousa SA, Dimitriadou V, Pepin MC, Wang T, et al. Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue. Clin Exp Metastasis. 2002;19(2):145-53.
Berbari P, Thibodeau A, Germain L, Saint-Cyr M, Gaudreau P, El-Khouri S, et al. Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. J Surg Res. 1999;87(1):108-13.
Chen L, Bao B, Wang N, Xie J, Wu W. Oral administration of shark type II collagen suppresses complete Freund’s adjuvant-induced rheumatoid arthritis in rats. Pharmaceuticals (Basel). 2012;5(4):339-52.
Laiyemo MA, Nunlee-Bland G, Adams RG, Laiyemo AO, Lombardo FA. Characteristics and health perceptions of complementary and alternative medicine users in the United States. Am J Med Sci. 2015;349(2):140-4.
Johnson SB, Park HS, Gross CP, James BY.Complementary medicine, refusal of conventional cancer therapy, and survival among patients with curable cancers. JAMA Oncol. 2018;4(10):1375-81.
Feyzi R, Hassan ZM, Mostafaie A. Modulation of CD4+ and CD8+ tumor infiltrating lymphocytes by a fraction isolated from shark cartilage: shark cartilage modulates anti-tumor immunity. Int Immunopharmacol. 2003;3(7):921-6.
Szadvári I, Krizanova O, Babula P. Athymic nude mice as an experimental model for cancer treatment. Physiol Res. 2016;65(Suppl 4):S441-53.
Falardeau P, Champagne P, Poyet P, Hariton C, Dupont É. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001;28(6):620-5.
Steele KE, Tan TH, Korn R, Dacosta K, Brown C, Kuziora M, et al. Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis. J Immunother Cancer. 2018;6(1):20.
Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017;545(7652):60-5.
Oikawa T, Ashino-Fuse H, Shimamura M, Koide U, Iwaguchi T. A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett. 1990;51(3):181-6.
Sheu JR, Fu CC, Tsai ML, Chung WJ. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res. 1998;18(6A):4435-41.
Liang JH, Wong KP. The characterization of angiogenesis inhibitor from shark cartilage. Adv Exp Med Biol.2000:476:209-23.
Kukreja I, Kapoor P, Deshmukh R, Kulkarni V. VEGF and CD 34: A correlation between tumor angiogenesis and microvessel density-an immunohistochemical study. J Oral Maxillofac Pathol. 2013;17(3):367-73.
Forster JC, Harriss-Phillips WM, Douglass MJ, Bezak E. A review of the development of tumor vasculature and its effects on the tumor microenvironment. Hypoxia (Auckl). 2017:5:21-32.
Dabbs DJ. Diagnostic immunohistochemistry e-book: theranostic and genomic applications. Elsevier Health Sciences; 2021 Nov 23.
Szafarowski T, Sierdzinski J, Szczepanski MJ, Whiteside TL, Ludwig N, Krzeski A. Microvessel density in head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2018;275(7):1845-51.
Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991;324(1):1-8.
Zargaran M, Eshghyar N, Baghaei F, Moghimbeigi A. Assessment of cellular proliferation in oral verrucous carcinoma and well-differentiated oral squamous cell carcinoma using Ki67: a non-reliable factor for differential diagnosis?. Asian Pac J Cancer Prev. 2012;13(11):5811-5.
Ragab HM, Samy N, Afify M, Abd El Maksoud N, Shaaban HM. Assessment of Ki-67 as a potential biomarker in patients with breast cancer. J Genet Eng Biotechnol. 2018;16(2):479-84
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