In vitro and in vivo antitumor effects of Peanut agglutinin through induction of apoptotic and autophagic cell death
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- 作者：Subhadip Mukhopadhyay ; Prashanta Kumar P ; a ; Birendra Behera ; Ch ; an Kanta Das ; Md Khurshidul Hassan ; Durgesh N ; ini Das ; Niharika Sinha ; Akalabya Bissoyi ; Krishna Pramanik ; Tapas K. Maiti ; Sujit K. Bhutia
- 关键词：Peanut agglutinin ; Apoptosis ; Autophagy ; ROS ; Senescence ; Dalton&rsquo ; s lymphoma
- 刊名：Food and Chemical Toxicology
- 出版年：February, 2014
- 年：2014
- 卷：64
- 期：Complete
- 页码：369-377
- 全文大小：1659 K
文摘
In this study we unravel the mechanism underlying the antitumorigenic effects of Peanut agglutinin (PNA) isolated from Arachis hypogea in Dalton鈥檚 lymphoma (DL) bearing mice and elucidated the mechanism in vitro in HeLa cells. In vivo PNA administration at 1 and 2 mg/kg body weight reduced DL proliferation with increase in autophagic and apoptotic characteristics. In vitro data showed that PNA at 0.1-100 渭g/ml dose exhibit selective antiproliferative activity on various cancer cell lines without displaying cytotoxic effect on normal cells. However, heat denatured PNA failed to show any antiproliferative activity. Moreover, PNA was found to induce autophagic and apoptotic cell death in HeLa cells. Exponential increase in reactive oxygen species (ROS) was proved to be the master signal for promoting PNA induced cell death in HeLa cells. Interestingly, when HeLa cells were pre-exposed with N-acetylcysteine (NAC) and followed to PNA treatment, there was sharp decline in autophagy, apoptosis and a concomitant abrogation of antiproliferative potential. PNA at lower doses was also seen to inflict senescence. Hence, this common culinary item derived molecule whose discovery dates back to late 1970s was for the first time evaluated mechanistically in vivo and in vitro as a novel naturally occurring therapeutic agent against cancer.