Cancer Biology Unit, Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625 021, India.
Department of Chemistry and Biosciences, SASTRA University, Srinivasa Ramanujan Centre (SRC), Kumbakonam, Tamil Nadu, 612001, India.
Mol Cell Biochem. 2018 Mar;440(1-2):11-22. doi: 10.1007/s11010-017-3151-5. Epub 2017 Aug 12.
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.
几十年来，尽管新的诊断和治疗策略不断发展，但口腔癌的生存率并没有提高。因此，本研究旨在探讨小白菊内酯在 DMBA 诱导的仓鼠颊囊癌变中的化学预防作用。将仓鼠分为 4 组（n=6/组）。第 1 组作为对照进行治疗。第 2 组和第 3 组在左侧颊囊上每周涂 3 次 0.5%的 DMBA，共 14 周。此外，第 3 组在涂 DMBA 的隔日口服小白菊内酯 2mg/kg 体重。第 4 组仅接受小白菊内酯治疗。第 14 周结束时，所有仓鼠均被处死。所有仓鼠的颊组织均进行组织病理学评估。使用对照和实验仓鼠的血浆、肝脏和颊黏膜进行生化研究。进行凋亡标志物 p53、Bcl-2 和 Bax 的基因和蛋白表达研究。结果显示，第 2 组仓鼠 100%形成肿瘤，并出现明显的组织病理学改变、解毒酶状态、脂质过氧化和抗氧化谱改变。小白菊内酯的口服给药完全阻止了肿瘤的形成，并显著降低了第 3 组仓鼠组织病理学变化的严重程度。与第 2 组仓鼠相比，小白菊内酯治疗组的解毒酶、脂质过氧化和抗氧化剂状态显著恢复。凋亡基因 p53 和抗凋亡基因 Bcl-2 明显下调，而促凋亡基因 Bax 在第 3 组仓鼠中上调。本研究结果表明，小白菊内酯对 DMBA 诱导的口腔癌变具有较强的化学预防、抗氧化和凋亡作用。
