Involvement of ROS in Curcumin-induced Autophagic Cell Death

Lee, Youn Ju; Kim, Nam‐Yi; Suh, Young Ah; Lee, ChuHee

doi:10.4196/kjpp.2011.15.1.1

Cited by 134 publications

(100 citation statements)

References 35 publications

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“…We found that curcumin treatment results in degradation of IKK and as a consequence, downregulation of NF-kB takes place in HuT-78 cells in a ROS-dependent manner. Earlier Zhang and colleagues reported that curcumin inhibits constitutive NF-kB in CTCL cells (15); but for the first time, we showed the Curcumin has been shown to induce autophagy in different cell types (29,30). It is also known that the IKK complex contributes to the induction of autophagy (31).…”

Section: Discussionmentioning

confidence: 89%

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Khan

Gahlot

Majumdar

2012

Molecular Cancer Therapeutics

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Curcumin is known to exert its anticancer effect either by scavenging or by generating reactive oxygen species (ROS). In this study, we report that curcumin-mediated rapid generation of ROS induces apoptosis by modulating different cell survival and cell death pathways in HuT-78 cells. Curcumin induces the activation of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but the addition of caspase inhibitors only partially blocked the curcumin-mediated apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c-FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS-dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF-kB. Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death. Mol Cancer Ther; 11(9); 1873-83. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 89%

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Khan

Gahlot

Majumdar

2012

Molecular Cancer Therapeutics

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“…Curcumin administered in combination with 5FU plus oxaliplatin resulted in increased inhibition of growth and enhanced apoptosis in HCT116 and HT29 colon cancer cells compared to each of these drugs alone, and these effects were attained mainly through the attenuation of the EGFR and IGF1R signaling pathways [136] . The induction of autophagy activation and ROS production was observed in HCT116 human colon cancer cells that were treated with curcumin, and they showed higher mRNA and protein LC3 levels [137] . Autophagy facilitates cancer cell resistance to chemo therapy treatments, and the inhibition of autophagy may resensitize resistant tumor cells to anticancer therapy, thus enhancing the efficacy of the treatment.…”

Section: Autophagy Drugs In Crcmentioning

confidence: 99%

Autophagy in colorectal cancer: An important switch from physiology to pathology

Burada

Nicoli

Ciurea

et al. 2015

WJGO

134

131

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Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of Core tip: This review describes the role of autophagy in cancer, focusing on the involvement of autophagy in colorectal cancer (CRC). Initially, we describe the steps and components of autophagy, and we then further highlight the dual role of autophagy in cancer, where it can potentially act as both a promoter and an inhibitor during the transformation from normal to malignant cell. In particular, we emphasize the major autophagy genes involved in CRC pathogenesis along with autophagymodulating agents and their modes of action in the context of CRC therapy. TOPIC HIGHLIGHT

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“…This is consistent with previous reports that both Dox and WFA as a monotherapy both produce ROS [156,157,175,178,179,190]. ROS-mediated autophagy has been observed in a number of different carcinoma cell lines [218][219][220].…”

Section: Discussionsupporting

confidence: 82%

“…Additionally, blocking ROS production with ROS scavengers and antioxidants reduced autophagic cell death is various solid tumors cell lines [220,221]. Mitochondrial ROS damage the mitochondrial membrane and result in leakage of ROS to the cytosol where they can damage other organelles as well as cause DNA damage and oxidation of amino acids and polydesatured fatty acids [222,223].…”

Section: Discussionmentioning

confidence: 99%

Development of pituitary tumor-transforming gene (PTTG) transgenic mice for the treatment of ovarian cancer.

Fong¹

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Involvement of ROS in Curcumin-induced Autophagic Cell Death

Cited by 134 publications

References 35 publications

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Autophagy in colorectal cancer: An important switch from physiology to pathology

Development of pituitary tumor-transforming gene (PTTG) transgenic mice for the treatment of ovarian cancer.

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