Abstract
Over the decades, the survival rates for oral cancer have not improved despite development in novel diagnostic and therapeutic strategies. Therefore, the present study is aimed at investigating the chemopreventive potential of parthenolide in DMBA-induced hamster buccal pouch carcinogenesis. The hamsters were divided into 4 groups (n = 6/group). Group I was treated as control. Groups II and III were painted with a solution of 0.5% DMBA three times per week for 14 weeks on the left buccal pouches. In addition, group III were orally administrated with parthenolide 2 mg/kg b.w on days alternate to the DMBA application. Group IV received only parthenolide. At the end of 14th week all hamsters were sacrificed. Buccal tissues from all hamsters were evaluated for histopathology. Biochemical studies were carried out using plasma, liver, and buccal mucosa of control and experimental hamsters. Gene and protein expression studies of apoptotic markers p53, Bcl-2, and Bax were performed. The results showed 100% tumor formation and marked alterations in histopathology, status of detoxification enzymes, lipid peroxidation, and antioxidant profile in group II hamsters. Oral administration of parthenolide completely prevented tumor formation and significantly reduced the severity of histopathological changes in group III hamsters. The status of detoxification enzymes, lipid peroxidation, and antioxidants were significantly restored in parthenolide treated group compared to group II hamsters. The apoptotic gene p53 and antiapoptotic gene Bcl-2 were significantly down regulated; whereas, pro-apoptotic gene Bax was up regulated in group III hamsters compared to group II. The results of the present study suggest that parthenolide have potent chemopreventive, antioxidant, and apoptotic effect in DMBA-induced oral carcinogenesis.
Similar content being viewed by others
References
Laprise C, Madathil SA, Allison P, Abraham P, Raghavendran A, Shahul HP, Thekke Purakkal AS, Castonguay G, Coutlee F, Schlecht NF, Rousseau MC (2016) No role for human papillomavirus infection in oral cancers in a region in southern India. Int J Cancer 138:912–917
Gupta B, Ariyawardana A, Johnson MM (2013) Oral cancer in India continues in epidemic proportions: evidence base and policy initiatives. Int Dent J 63:12–25
Wang ZQ, Liu K, Huo ZJ, Li XC, Wang M, Liu P, Pang B, Wang SJA (2015) Cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell carcinoma therapy. J Nanobiotechnol 13:63
Ray G, Husain SA (2002) Oxidants, antioxidants and carcinogenesis. Indian J Exp Biol 40:1213–1232
Guven M, Ozturk B, Sayal A, Ozet A (2000) Lipid peroxidation and antioxidant system in the blood of patients with Hodgkin’s disease. Clin Biochem 33:209–212
Patel BP, Rawal UM, Dave TK, Rawal RM, Shukla SN, Shah PM, Patel PS (2007) Lipid peroxidation, total antioxidant status, and total thiol levels predict overall survival in patients with oral squamous cell carcinoma. Integr Cancer Ther 6:365–372
Manikandan P, Letchoumy PV, Gopalakrishnan M, Nagini S (2008) Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and in vivo modulation of biomarkers of chemoprevention in the hamster buccal pouch carcinogenesis model. Food Chem Toxicol 46:2332–2343
Anand MA, Suresh K (2014) Biochemical profiling and chemopreventive activity of phloretin on 7,12-dimethylbenz(a) anthracene induced oral carcinogenesis in male golden Syrian hamsters. Toxicol Int 21:179–185
Goulart Filho JA, Nonaka CF, da Costa Miguel MC, de Almeida Freitas R, Galvao HC (2009) Immunoexpression of cyclooxygenase-2 and p53 in oral squamous cell carcinoma. Am J Otolaryngol 30:89–94
Vinothkumar V, Manoharan S, Sindhu G, Nirmal MR, Vetrichelvi V (2012) Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 369:17–25
Garg R, Ingle A, Maru G (2008) Dietary turmeric modulates DMBA-induced p21ras, MAP kinases and AP-1/NF-kappaB pathway to alter cellular responses during hamster buccal pouch carcinogenesis. Toxicol Appl Pharmacol 232:428–439
Baskaran N, Manoharan S, Balakrishnan S, Pugalendhi P (2010) Chemopreventive potential of ferulic acid in 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in Sprague–Dawley rats. Eur J Pharmacol 637:22–29
Silvan S, Manoharan S (2013) Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Arch Oral Biol 58:94–101
Knight DW (1995) Feverfew: chemistry and biological activity. Nat Prod Rep 12:271–276
Jain NK, Kulkarni SK (1999) Antinociceptive and antiinflammatory effects of Tanacetum parthenium L. extract in mice and rats. J Ethnopharmacol 68:251–259
Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM (2001) The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol 8:759–766
Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Diaz JA, de Souza W, Nakamura CV (2005) Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium. Antimicrob Agents Chemother 49:176–182
Herrera F, Martin V, Rodriguez-Blanco J, García-Santos G, Antolin I, Rodriguez C (2005) Intracellular redox state regulation by parthenolide. Biochem Biophys Res Commun 332:321–325
Lesiak K, Koprowska K, Zalesna I, Nejc D, Duchler M, Czyz M (2010) Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro. Melanoma Res 20:21–34
Mohsenzadeh F, Chehregani A, Amiri H (2011) Chemical composition, antibacterial activity and cytotoxicity of essential oils of Tanacetum parthenium indifferent developmental stages. Pharm Biol 49:920–926
Mathema VB, Koh YS, Thakuri BC, Sillanpaa M (2012) Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation 35:560–565
Yang Q, Wan L, Zhou Z, Li Y, Yu Q, Liu L, Li B, Guo C (2013) Parthenolide from Parthenium integrifolium reduces tumor burden and alleviate cachexia symptoms in the murine CT-26 model of colorectal carcinoma. Phytomedicine 20:992–998
Lu C, Wang W, Jia Y, Liu X, Tong Z, Li B (2014) Inhibition of AMPK/autophagy potentiates parthenolide-induced apoptosis in human breast cancer cells. J Cell Biochem 115:1458–1466
Al-Fatlawi AA, Al-Fatlawi AA, Irshad Rahisuddin M, Ahmad A (2015) Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell line. Pharm Biol 53:104–109
Omura T, Sato R (1964) The carbon monoxide binding pigment of liver microsomes. J Biol Chem 239:2370–2378
Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490
Habig WH, Pabst MJ, Jakoby WB (1974) WBC glutathione-S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Ernster L (1967) DT-Diaphorase. In: Estabrook RW, Pullman ME (eds) Methods enzymol, vol 10. Academic Press, New York, pp 309–317
Yagi K (1987) Lipid peroxides and human diseases. Chem Phys Lipids 45:337–351
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Beutler E, Kelly BM (1963) The effect of sodium nitrite on red cell GSH. Experientia 19:96–97
Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27:502–522
Desai ID (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol 105:138–147
Palan PR, Mikhail MS, Basu J, Romney SL (1991) Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dysplasias and cancer. Nutr Cancer 15:13–20
Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132
Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394
Rotruck JT, Pope AL, Ganther HE et al (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590
Sasikumar P, Gomathi S, Anbazhagan K, Abhishek A, Paul E, Vasudevan V, Sasikumar S, Selvam GS (2014) Recombinant Lactobacillus plantarum expressing and secreting heterologous oxalate decarboxylase prevents renal calcium oxalate stone deposition in experimental rats. J Biomed Sci 21:86
Nagini S, Letchoumy PV, Cr TR (2009) Of humans and hamsters: a comparative evaluation of carcinogen activation, DNA damage, cell proliferation, apoptosis, invasion, and angiogenesis in oral cancer patients and hamster buccal pouch carcinomas. Oral Oncol 45:31–37
Nakagawa K, Yamamura K, Maeda S, Ichihashi M (1994) Bcl-2 expression in epidermal keratinocytic diseases. Cancer 74:1720–1724
Manoharan S, Vasanthaselvan M, Silvan S, Baskaran N, Kumar Singh A, Vinoth Kumar V (2010) Carnosic acid: a potent chemopreventive agent against oral carcinogenesis. Chem Biol Interact 188:616–622
Silvan S, Manoharan S, Baskaran N, Anusuya C, Karthikeyan S, Prabhakar MM (2011) Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis. Eur J Pharmacol 670:571–577
Hayashi S, Koshiba K, Hatashita M, Sato T, Jujo Y, Suzuki R, Tanaka Y, Shioura H (2011) Thermosensitization and induction of apoptosis or cell-cycle arrest via the MAPK cascade by parthenolide, an NF-kappaB inhibitor, in human prostate cancer androgen- independent cell lines. Int J Mol Med 28:1033–1042
DAnneo A, Carlisi D, Lauricella M, Puleio R, Martinez R, Di Bella S, Di Marco P, Emanuele S, Di Fiore R, Guercio A, Vento R, Tesoriere G (2013) Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer. Cell Death Dis 4:891
Yu HJ, Jung JY, Jeong JH, Cho SD, Lee JS (2015) Induction of apoptosis by parthenolide in human oral cancer cell lines and tumor xenografts. Oral Oncol 51:602–609
Zhao X, Liu X, Su L (2014) Parthenolide induces apoptosis via TNFRSF10B and PMAIP1 pathways in human lung cancer cells. J Exp Clin Cancer Res 33:3
Koprowska K, Czyz M (2010) Molecular mechanisms of parthenolide’s action: old drug with a new face. Postepy Hig Med Dosw 64:100–114
Rajasekaran D, Manoharan S, Prabhakar MM, Manimaran A (2015) Enicostemma littorale prevents tumor formation in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. Hum Exp Toxicol 34:911–921
Acknowledgements
Financial support from University Grants Commission (UGC), New Delhi to Dr. N. Baskaran in the form of UGC-Post Doctoral Fellow (Ref: No. F./PDFSS-2013-14-SC-TAM-4741 dt. On 03/07/2014) is gratefully acknowledged. Further, Author gratefully acknowledged to Dr.G.S.Selvam, Professor and Head, Department of Biochemistry, Madurai Kamaraj University, Madurai for his valuable guidance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that there are no conflicts of interest.
Rights and permissions
About this article
Cite this article
Baskaran, N., Selvam, G.S., Yuvaraj, S. et al. Parthenolide attenuates 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 440, 11–22 (2018). https://doi.org/10.1007/s11010-017-3151-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-017-3151-5