Tumor growth retardation and chemosensitizing action of fatty acid synthase inhibitor orlistat on T cell lymphoma: Implication of reconstituted tumor microenvironment and multidrug resistance phenotype

Kant, Shri; Kumar, Ajay; Singh, Sukh Mahendra

doi:10.1016/j.bbagen.2013.09.020

Cited by 43 publications

(46 citation statements)

References 51 publications

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“…We also found that orlistat increased cellular ROS level and induced the expression of the cell stress proteins BIP and PERK. Previous studies in other cancer cell lines and animal studies have also shown that orlistat can induce cell stress and decrease cell proliferation, similar to our findings in endometrial cancer [20][21][22]. Our results suggest that cell cycle arrest and cellular stress also contributed to a decrease in endometrial cancer cell proliferation in response to orlistat.…”

Section: Discussionsupporting

confidence: 93%

“…Previous reports have shown that orlistat can induce cell stress in lymphoma and prostate cancer [20][21][22], so we investigated whether induction of cellular stress could be a mechanism through which orlistat decreases endometrial cancer cell proliferation. Orlistat increased ROS levels in both cell lines in a dosedependent fashion ( Fig.…”

Section: Orlistat Induces Cell Stress In Endometrial Cancer Cell Linesmentioning

confidence: 99%

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Effects of Fatty Acid Synthase Inhibition by Orlistat on Proliferation of Endometrial Cancer Cell Lines

et al. 2016

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Section: Discussionsupporting

confidence: 93%

Section: Orlistat Induces Cell Stress In Endometrial Cancer Cell Linesmentioning

confidence: 99%

Effects of Fatty Acid Synthase Inhibition by Orlistat on Proliferation of Endometrial Cancer Cell Lines

et al. 2016

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“…Increase production of ROS after orlistat administration has been implicated in the elevation of IFN-γ, which manifests induction of apoptosis through inhibition of FASN expression in Dalton's lymphoma-transplanted BALB/c mice [57]. Indeed, over production of ROS in cancer cells causes impairment of cellular redox homeostasis inducing oxidative stress that consequently can make cancer cells more susceptible to oxidative stress than normal cells, which effectively balance the redox system [3], [6].…”

Section: Discussionmentioning

confidence: 99%

The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells

et al. 2014

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The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs) by blocking the fatty acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm). Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS) generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting FASN protein in HepG2 cells.

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“…The current understanding about chemotherapy suggests that the induction of apoptosis in target cells is a key mechanism for various anticancer drugs [21,22]. Cell apoptosis is a complex process that may be achieved through activation of a cascade of intracellular factors known as caspases [23][24][25].…”

Section: Mirnas Regulate Cell Apoptosis-related Proteinsmentioning

confidence: 99%

Drug resistance-related microRNAs in hematological malignancies: Translating basic evidence into therapeutic strategies

Xie

Jing

et al. 2015

Blood Reviews

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Tumor growth retardation and chemosensitizing action of fatty acid synthase inhibitor orlistat on T cell lymphoma: Implication of reconstituted tumor microenvironment and multidrug resistance phenotype

Cited by 43 publications

References 51 publications

Effects of Fatty Acid Synthase Inhibition by Orlistat on Proliferation of Endometrial Cancer Cell Lines

Effects of Fatty Acid Synthase Inhibition by Orlistat on Proliferation of Endometrial Cancer Cell Lines

The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells

Drug resistance-related microRNAs in hematological malignancies: Translating basic evidence into therapeutic strategies

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