02581nas a2200277   4500008004100000022001400041245012800055210006900183260008100252300002000333490000700353520154700360653001501907653001601922653002901938653001401967100002201981700002102003700002402024700002902048700002302077700002902100700002502129700002302154856012602177       2014                        eng d  a1476-459800aCholesterol depletion by methyl-beta-cyclodextrin augments tamoxifen induced cell death by enhancing its uptake in melanoma0 aCholesterol depletion by methylbetacyclodextrin augments tamoxif  a236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLANDbBIOMED CENTRAL LTDcSEP  aArticle No. 2040 v133 a<p>Background: Despite modern advances in treatment, skin cancer is still one of the most common causes of death in the western countries. Chemotherapy plays an important role in melanoma management. Tamoxifen has been used either alone or in-combination with other chemotherapeutic agents to treat melanoma. However, response rate of tamoxifen as a single agent has been comparatively low. In the present study, we investigated whether treatment with methyl-beta-cyclodextrin (MCD), a cholesterol depleting agent, increases the efficacy of tamoxifen in melanoma cells. Methods: This was a two-part study that incorporated in vitro effects of tamoxifen and MCD combination by analyzing cell survival, apoptosis and cell cycle analysis and in vivo antitumor efficacy on tumor isografts in C57BL/6J mice. Results: MCD potentiated tamoxifen induced anticancer effects by causing cell cycle arrest and induction of apoptosis. Sensitization to tamoxifen was associated with down regulation of antiapoptotic protein Bcl-2, up-regulation of proapoptotic protein Bax, reduced caveolin-1 (Cav-1) and decreased pAkt/pERK levels. Co-administration of tamoxifen and MCD caused significant reduction in tumor volume and tumor weight in mice due to enhancement of drug uptake in the tumor. Supplementation with cholesterol abrogated combined effect of tamoxifen and MCD. Conclusion: Our results emphasize a potential synergistic effect of tamoxifen with MCD, and therefore, may provide a unique therapeutic window for improvement in melanoma treatment.</p>10aCaveolin-110aCholesterol10aMethyl beta-cyclodextrin10aTamoxifen1 aMohammad, Naoshad1 aMalvi, Parmanand1 aMeena, Avtar, Singh1 aSingh, Shivendra, Vikram1 aChaube, Balkrishna1 aVannuruswamy, Garikapati1 aKulkarni, Mahesh, J.1 aBhat, Manoj, Kumar  uhttps://library.ncl.res.in/content/cholesterol-depletion-methyl-beta-cyclodextrin-augments-tamoxifen-induced-cell-death-0