Inhibitory effect of Solanum xanthocarpum on the growth of KB human oral cancer cell line in vitro through ROS-induced mitochondrial pathway
The aim of the present study was to investigate the effect of Solanum xanthocarpum on KB human oral cancer cells by analyzing its anti-proliferative and apoptotic properties as well as its inhibitory effect on cell adhesion. In this study, the leaves extract of S. xanthocarpum was prepared using the maceration method. Cytotoxic effect of different doses of the S. xanthocarpum extract was assessed using MTT assay. Measurements of reactive oxygen species (ROS), lipid peroxidation and antioxidant enzymes were also performed. In addition, we also studied the impacts of S. xanthocarpum on the apoptosis and mitochondrial membrane potential of KB cells. Determination of antioxidant enzymes and lipid peroxidation was performed using biochemical methods. The S. xanthocarpum showed cytotoxic activity against KB cells with IC50 (200 μg/mL). Besides, DCFH-DA staining and acridine orange/ethidium bromide staining results demonstrated that S. xanthocarpum induced the generation of ROS and apoptosis in KB cells, respectively. Based on the Rh-123 staining results, S. xanthocarpum decreased mitochondrial depolarization in KB cells. Furthermore, the S. xanthocarpum treatment contributed to increased lipid peroxidation, accompanied by reduced activities of superoxide dismutase and catalase, as well as decreased glutathione content. Taken together, these findings indicate that S. xanthocarpum extract might comprise bioactive compounds of therapeutic significance, which can inhibit the growth of KB cells.
Pires FR, Ramos AB, Oliveira JB, et al., 2013, Oral squamous cell carcinoma: Clinicopathological features from 346 cases from a single oral pathology service during an 8-year period. J Appl Oral Sci, 21: 460–467. https://doi.org/10.1590/1679-775720130317
D’souza S, Addepalli V, 2018, Preventive measures in oral cancer: An overview. Biomed Pharmacother, 107: 72–80. https://doi.org/10.1016/j.biopha.2018.07.114
Mohan M, Jagannathan N, 2014, Oral field cancerization: An update on current concepts. Oncol Rev, 8: 244. https://doi.org/10.4081/oncol.2014.244
Park S, 2018, Mechanical alteration associated with chemotherapeutic resistance of breast cancer cells. J Cancer Prev, 23: 87–92. https://doi.org/10.15430/jcp.2018.23.2.87
Bussmann RW, 2013, The globalization of traditional medicine in northern peru: From shamanism to molecules. Evid Based Complement Alternat Med, 2013: 291903. https://doi.org/10.1155/2013/291903
Fridlender M, Kapulnik Y, Koltai H, 2015, Plant derived substances with anti-cancer activity: From folklore to practice. Front Plant Sci, 6: 799. https://doi.org/10.3389/fpls.2015.00799
Yin SY, Wei WC, Jian FY, et al., 2013, Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med, 2013: 302426.
Lin HM, Tseng HC, Wang CJ, et al., 2007, Induction of autophagy and apoptosis by the extract of Solanum nigrum Linn in HepG2 cells. J Agric Food Chem, 55: 3620–3628. https://doi.org/10.1021/jf062406m
Aye MM, Aung HT, Sein MM, et al., 2019, A review on the phytochemistry, medicinal properties and pharmacological activities of 15 selected myanmar medicinal plants. Molecules, 24: E293. https://doi.org/10.3390/molecules24020293
Chang LC, Tsai TR, Wang JJ, et al., 1998, The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis. Biochem Biophys Res Commun, 242: 21–25. https://doi.org/10.1006/bbrc.1997.7903
Gurunathan S, Qasim M, Park C, et al., 2018, Cytotoxic potential and molecular pathway analysis of silver nanoparticles in human colon cancer cells HCT116. Int J Mol Sci, 19: E2269. https://doi.org/10.3390/ijms19082269
Mosmann T, 1983, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods, 65: 55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Liu K, Liu PC, Liu R, et al., 2015, Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Med Sci Monit Basic Res, 21: 15–20. https://doi.org/10.12659/msmbr.893327
Beyer WF, Fridovich I, 1987, Assaying for superoxide dismutase activity: Some large consequences of minor changes in conditions. Anal Biochem, 161: 559–566. https://doi.org/10.1016/0003-2697(87)90489-1
Aebi H, 1984, Catalase in vitro. Methods Enzymol, 105: 121–126.
Griffith OW, 1980, Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem, 106: 207–212. https://doi.org/10.1016/0003-2697(80)90139-6
Ohkawa H, Ohishi N, Yagi K, 1979, Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95: 351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Cheng YT, Yang CC, Shyur LF, 2016, Phytomedicine-modulating oxidative stress and the tumor microenvironment for cancer therapy. Pharmacol Res, 114: 128–143. https://doi.org/10.1016/j.phrs.2016.10.022
Altemimi A, Lakhssassi N, Baharlouei A, et al., 2017, Phytochemicals: Extraction, isolation, and identification of bioactive compounds from plant extracts. Plants (Basel), 6: E42. https://doi.org/10.3390/plants6040042
Kumar S, Pandey AK, 2014, Medicinal attributes of Solanum xanthocarpum fruit consumed by several tribal communities as food: An in vitro antioxidant, anticancer and anti HIV perspective. BMC Complement Altern Med, 14: 112. https://doi.org/10.1186/1472-6882-14-112
Mirzayans R, Andrais B, Murray D, 2018, Viability assessment following anticancer treatment requires single-cell visualization. Cancers (Basel), 10: E255. https://doi.org/10.3390/cancers10080255
Florento L, Matias R, Tuaño E, et al., 2012, Comparison of cytotoxic activity of anticancer drugs against various human tumor cell lines using in vitro cell-based approach. Int J Biomed Sci, 8: 76–80.
Zhang P, Wang P, Yan L, et al., 2018, Synthesis of gold nanoparticles with Solanum xanthocarpum extract and their in vitro anticancer potential on nasopharyngeal carcinoma cells. Int J Nanomed, 13: 7047–7059. https://doi.org/10.2147/ijn.s180138
Nita M, Grzybowski A, 2016, The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid Med Cell Longev, 2016: 3164734. https://doi.org/10.1155/2016/3164734
Kumar S, Sharma UK, Sharma AK, et al., 2012, Protective efficacy of Solanum xanthocarpum root extracts against free radical damage: Phytochemical analysis and antioxidant effect. Cell Mol Biol (Noisy-le-grand), 58: 174–181.
Vijayalakshmi A, Sindhu G, 2017, Umbelliferone arrest cell cycle at G0/G1 phase and induces apoptosis in human oral carcinoma (KB) cells possibly via oxidative DNA damage. Biomed Pharmacother, 92: 661–671. https://doi.org/10.1016/j.biopha.2017.05.128
Jin Z, El-Deiry WS, 2005, Overview of cell death signaling pathways. Cancer Biol Ther, 4(2): 139–163.
Kurutas EB, 2016, The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. Nutr J, 15: 71. https://doi.org/10.1186/s12937-016-0186-5
Yang NJ, Hinner MJ, 2015, Getting across the cell membrane: An overview for small molecules, peptides, and proteins. Methods Mol Biol, 1266: 29–53. https://doi.org/10.1007/978-1-4939-2272-7_3
Lobo V, Patil A, Phatak A, et al., 2010, Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev, 4: 118–126. https://doi.org/10.4103/0973-7847.70902
Ullah A, Munir S, Badshah SL, et al., 2020, Important flavonoids and their role as a therapeutic agent. Molecules (Basel, Switzerland), 25: 5243. https://doi.org/10.3390/molecules25225243