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Methanol extracts of Humulus japonicus induced apoptosis in human FaDu hypopharynx squamous carcinoma cells

  • Jang, Ji Yeon (Department of Oral Biochemistry, College of Dentistry, Chosun University) ;
  • Park, Bo-Ram (Department of Dental Hygiene, College of Health and Welfare, Kyungwoon University) ;
  • Lee, Seul Ah (Department of Oral Biochemistry, College of Dentistry, Chosun University) ;
  • Choi, Mi Suk (Department of Dental Hygiene, Chodang University) ;
  • Kim, Chun Sung (Department of Oral Biochemistry, College of Dentistry, Chosun University)
  • Received : 2022.03.04
  • Accepted : 2022.03.16
  • Published : 2022.03.31

Abstract

Humulus japonicus (HJ) is a widely used herbal medicine for pulmonary tuberculosis, hypertension, leprosy, and venomous wounds in Asia, particularly in China. Although HJ has certain physiological activities, such as longitudinal bone growth, antioxidation and alleviation of rheumatism, its anticancer activities, other than in colorectal and ovarian cancer, are yet to be studied. In this study, we investigated the anti-cancer activity and mechanism of methanol extracts of HJ (MeHJ) against human FaDu hypopharyngeal squamous carcinoma cells. MeHJ suppressed FaDu cell viability without affecting normal cells (L929), which was demonstrated using the MTT and Live & Dead assays. Furthermore, MeHJ effectively inhibited colony formation of FaDu cells, even at non-cytotoxic concentrations, and significantly induced apoptosis through the proteolytic cleavage of caspase-9, -3, -7, poly (ADP-ribose) polymerase and through the downregulation of BCL-2 and upregulation of BAX in FaDu cells, as determined by DAPI staining, flow cytometry, and western blot analyses. Collectively, these findings suggest that the inhibitory effects of MeHJ on the growth and colony formation of oral cancer cells may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeHJ has the potential to be used as a natural chemotherapeutic drug against human oral cancer.

Keywords

Acknowledgement

This study was supported by a research fund from Chosun University, 2021.

References

  1. Zhu C, Gu L, Yao M, Li J, Fang C. Prognostic value of an immune-related gene signature in oral squamous cell carcinoma. Front Oncol 2021;11:776979. doi: 10.3389/fonc.2021.776979.
  2. Kim J. The anti-cancer effect of betulin derived from the outer bark of birch on head and neck squamous cell carcinoma. J Adv Eng Technol 2020;13:131-7. https://doi.org/10.35272/JAET.2020.13.3.131
  3. Lee JG, Park SJ, Kim SC, Jee SY. Coptidis Rhizoma extract induces apoptotic cell death in YD-10B cell. J Korean Orient Med Ophthalmol Otolaryngol Dermatol 2009;22:50-9.
  4. Kameyanda Poonacha S, Harishkumar M, Radha M, Varadarajan R, Nalilu SK, Shetty SS, Shetty PK, Chandrashekharappa RB, Sreenivas MG, Bhandary Bavabeedu SK. Insight into oroxylinA-7-O-β-d-glucuronide-enriched Oroxylum indicum bark extract in oral cancer HSC-3 cell apoptotic mechanism: role of mitochondrial microenvironment. Molecules 2021;26:7430. doi: 10.3390/molecules26247430.
  5. Sasi M, Kumar S, Kumar M, Thapa S, Prajapati U, Tak Y, Changan S, Saurabh V, Kumari S, Kumar A, Hasan M, Chandran D, Radha, Bangar SP, Dhumal S, Senapathy M, Thiyagarajan A, Alhariri A, Dey A, Singh S, Prakash S, Pandiselvam R, Mekhemar M. Garlic (Allium sativum L.) bioactives and its role in alleviating oral pathologies. Antioxidants (Basel) 2021;10:1847. doi: 10.3390/antiox10111847.
  6. Lee SA, Park BR, Kim CS. Trifolium pratense induces apoptosis through caspase pathway in FaDu human hypopharynx squamous carcinoma cells. Int J Oral Biol 2019;44:81-8. doi: 10.11620/IJOB.2019.44.3.81.
  7. Park TS, Ryu YK, Park HY, Kim JY, Go J, Noh JR, Kim YH, Hwang JH, Choi DH, Oh WK, Lee CH, Kim KS. Humulus japonicus inhibits the progression of Alzheimer's disease in a APP/PS1 transgenic mouse model. Int J Mol Med 2017;39: 21-30. doi: 10.3892/ijmm.2016.2804.
  8. Chae J, Jo H, Yeom H, Lee J. Antioxidation and functional cosmetics activity of Humulus japonicus Sieboid & Zucc. according to collection time and extraction solvent. J Korean Soc For Sci. 2021;110:254-65. doi: 10.14578/jkfs.2021.110.2.254.
  9. Lee YR, Kim KY, Lee SH, Kim MY, Park HJ, Jeong HS. Antioxidant and antitumor activities of methanolic extracts from Humulus japonicus. Korean J Food Nutr 2012;25:357-61. doi: 10.9799/ksfan.2012.25.2.357.
  10. Nam EJ, Yoo G, Lee JY, Kim M, Jhin C, Son YJ, Kim SY, Jung SH, Nho CW. Glycosyl flavones from Humulus japonicus suppress MMP-1 production via decreasing oxidative stress in UVB irradiated human dermal fibroblasts. BMB Rep 2020;53:379-84. doi: 10.5483/BMBRep.2020.53.7.253.
  11. Kang EJ, Kim HJ, Choi JH, Noh JR, Kim JH, Lee IB, Choi YK, Choi DH, An J, Oh WK, Kim YH, Lee CH. Humulus japonicus extract ameliorates collagen-induced arthritis in mice through regulation of overall articular inflammation. Int J Mol Med 2020;45:417-28. doi: 10.3892/ijmm.2019.4417.
  12. Sung B, Chung JW, Bae HR, Choi JS, Kim CM, Kim ND. Humulus japonicus extract exhibits antioxidative and anti-aging effects via modulation of the AMPK-SIRT1 pathway. Exp Ther Med 2015;9:1819-26. doi: 10.3892/etm.2015.2302.
  13. Park SW, Woo CJ, Chung SK, Chung KT. Antimicrobial and antioxidative activities of solvent fraction from Humulus japonicus. Korean J Food Sci Technol 1994;26:464-70.
  14. Lim H, Noh JR, Kim YH, Hwang JH, Kim KS, Choi DH, Go MJ, Han SS, Oh WK, Lee CH. Anti-atherogenic effect of Humulus japonicus in apolipoprotein E-deficient mice. Int J Mol Med 2016;38:1101-10. doi: 10.3892/ijmm.2016.2727.
  15. Park JW, Ko SH, Kim CW, Jeoung BJ, Hong CS. Identification and characterization of the major allergen of the Humulus japonicus pollen. Clin Exp Allergy 1999;29:1080-6. doi: 10.1046/j.1365-2222.1999.00615.x.
  16. Kim OK, Yun JM, Lee M, Park SJ, Kim D, Oh DH, Kim HS, Kim GY. A mixture of Humulus japonicus increases longitudinal bone growth rate in Sprague Dawley rats. Nutrients 2020;12:2625. doi: 10.3390/nu12092625.
  17. Bae J, Min YS, Nam Y, Lee HS, Sohn UD. Humulus japonicus extracts protect against lipopolysaccharide/d-galactosamine-induced acute liver injury in rats. J Med Food 2018;21:1009-15. doi: 10.1089/jmf.2018.4178.
  18. Yu BC, Yang MC, Lee KH, Kim KH, Choi SU, Lee KR. Two new phenolic constituents of Humulus japonicus and their cytotoxicity test in vitro. Arch Pharm Res 2007;30:1471-5. doi: 10.1007/BF02977373.
  19. Links M, Lewis C. Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs 1999;57:293-308. doi: 10.2165/00003495-199957030-00003.
  20. Smets LA. Programmed cell death (apoptosis) and response to anti-cancer drugs. Anticancer Drugs 1994;5:3-9. doi: 10.1097/00001813-199402000-00001.
  21. Mukherjee AK, Basu S, Sarkar N, Ghosh AC. Advances in cancer therapy with plant based natural products. Curr Med Chem 2001;8:1467-86. doi: 10.2174/0929867013372094.
  22. Su Z, Yang Z, Xu Y, Chen Y, Yu Q. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer 2015;14:48. doi: 10.1186/s12943-015-0321-5.
  23. Guchhait KC, Manna T, Barai M, Karmakar M, Nandi SK, Jana D, Dey A, Panda S, Raul P, Patra A, Bhattacharya R, Chatterjee S, Panda AK, Ghosh C. Antibiofilm and anticancer activities of unripe and ripe Azadirachta indica (neem) seed extracts. BMC Complement Med Ther 2022;22:42. doi: 10.1186/s12906-022-03513-4.
  24. Lim HM, Lee J, Nam MJ, Park SH. Acetylshikonin induces apoptosis in human colorectal cancer HCT-15 and LoVo cells via nuclear translocation of FOXO3 and ROS level elevation. Oxid Med Cell Longev 2021;2021:6647107. doi: 10.1155/2021/6647107.
  25. Lee H, Oh C, Kim S, Dey DK, Kim HK, Bajpai VK, Han YK, Huh YS. Metasequoia glyptostroboides potentiates anticancer effect against cervical cancer via intrinsic apoptosis pathway. Sci Rep 2021;11:894. doi: 10.1038/s41598-020-79573-8.