Pre-treatment: Dietary Supplements/Cisplatin

# C311 Pretreatment with -carotene, retinoic acid, quercetin and genistein enhances the apoptosis induced by cisplatin in HeP2 cells by down-regulation of antiapoptotic proteins.

Himani Sharma, Sudip Sen and Neeta Singh, All India Institute of Medical Sciences, New Delhi, India.

Relatively little is known about the effect of dietary factors on the toxicity of chemotherapeutic agents. Though epidemiological data suggests that these nutrient factors obtained from fruits and vegetables play an important chemopreventive role.

Apoptosis is an important mechanism by which chemotherapeutic drugs kill tumor cells; hence, a better understanding of the molecular mechanisms involved in the process is needed.

The objective of this study was to investigate whether the efficacy of the chemotherapeutic agent Cisplatin generally used for head and neck cancers can be enhanced by pretreatment with -carotene, Retinoic acid, Quercetin and Genistein in human laryngeal carcinoma HeP2 cells.

Morphological examination, Flowcytometry and TUNEL were used for detection of apoptosis. Expression of the antiapoptotic proteins Bcl-2, Bcl-XL and Survivin, a member of Inhibitor of Apoptosis (IAP) family was seen by Western blotting.

The results indicate that a similar level of apoptosis (55-70%) can be achieved with lower, less toxic dose of Cisplatin if priming is done with these dietary factors 24 hours prior to Cisplatin treatment. Cisplatin (5 g/ml) treatment for 24 hours led to 70-80% apoptosis whereas pretreatment with these dietary factors for 24 hours prior to Cisplatin treatment at a much lower dose (1.5 g/ml) can result in similar percentage of apoptosis as seen with the higher dose.

The findings indicate that Cisplatin alone at the dose of 2.5 g/ml and 5 g/ml did not significantly reduce the levels of the antiapoptotic proteins. However, when a dose of 1.5 g/ml was given after priming with dietary factors, a significant decrease in the expression of these proteins was observed thereby sensitizing the HeP2 cells to apoptosis.

Priming the HeP2 cells with these dietary factors thus helps to reduce the dose of Cisplatin used (1.5 g/ml) to achieve similar percentage of apoptosis as is seen with a higher dose (5 g/ml) of Cisplatin.

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