Potential of diallyl sulfide bearing pH-sensitive liposomes in chemoprevention against DMBA-induced skin papilloma
Potential of diallyl sulfide bearing pH-sensitive liposomes in chemoprevention against DMBA-induced skin papilloma
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DOI：
10.2119/2006-00111.khan
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发表时间：
2007-07-01
影响因子：
5.7
通讯作者：
Owais, Mohammad
中科院分区：
文献类型：
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作者：
Khan, Arif;Shukla, Yogeshwer;Owais, Mohammad
二烯丙基硫醚（DAS），大蒜的活性成分，具有很强的抗肿瘤特性，对各种形式的癌症。在本研究中，我们评价了脂质体化DAS（常规卵PC和pH敏感性脂质体）对DMBA诱导的皮肤乳头状瘤的化学预防作用。在暴露于DMBA（52 μ g/小鼠/剂量）1小时后，将各种基于脂质体的DAS新制剂（250 μ g/小鼠）局部应用于动物。动物每周给药三次，共持续12周。基于诸如肿瘤发生率和诱导的肿瘤结节的总数和大小的参数来评价DAS的各种脂质体制剂的功效。还评估了脂质体化DAS制剂对p53 wt、p53 mut和p21/Waf 1表达的影响。本研究结果表明，脂质体DAS能有效地延缓肿瘤的发生，并减少肿瘤的累积数量和大小。用DAS脂质体制剂治疗DMBA暴露的动物，随后上调p53 wf和p21/Waf 1，而p53 mut表达水平降低。脂质体DAS的有前途的化学预防性质可以形成建立控制各种形式的癌症（包括皮肤乳头状瘤）的有效手段的基础。
Diallyl sulfide (DAS), an active component of garlic, possesses strong anti-neoplastic properties against various forms of cancer. In the present study, we have evaluated chemo-preventive effects of liposomized DAS (conventional egg PC and pH-sensitive liposomes) against DMBA-induced skin papilloma, Various liposome-based novel formulations of DAS (250 mu g/mouse) were applied topically, after one hour of exposure to DMBA (52 mu g/mouse/dose), to the animals. The animals were treated thrice weekly for the total period of 12 weeks. The efficacy of the various liposomal formulations of DAS was evaluated on the basis of parameters such as incidence of tumorogeness and total numbers and sizes of induced tumor nodules. The liposomized DAS formulations also were assessed for their effect on the expression of p53wt, p53mut, and p21/Waf1. The results of the present study showed that liposomized DAS could effectively delay the onset of tumorogenesis and reduce the cumulative numbers and sizes of tumor papillomas in treated mice, Treatment of DMBA-exposed animals with the liposomal formulation of DAS ensued in up-regulation of p53wf and p21/Waf1, while levels of p53mut expression reduced down. The promising chemo-preventive nature of liposomal DAS may form the basis for establishing effective means of controlling various forms of cancer, including skin papilloma.