Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells

Li, Bin; Takeda, Takashi; Tsuiji, Kenji; Wong, Tze Fang; Tadakawa, Mari; Kondo, Akiko; Nagase, Satoru; Yaegashi, Nobuo

doi:10.1097/igc.0b013e31828c9581

Cited by 43 publications

(31 citation statements)

References 24 publications

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“…Besides apoptosis, curcumin induces caspase-3 independent apoptosis (autophagy) in cancer cells (15). Autophagy culminates in either cell death or survival/quiescence/differentiation of tumor cells (15,21,35). Curcumin induced autophagy in cancer cells is mainly reported to result in cell death (12,18).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy culminates in either cell death or survival/quiescence/differentiation of tumor cells (15,21,35). Curcumin induced autophagy in cancer cells is mainly reported to result in cell death (12,18). Our results, however, suggest that while curcumin induces apoptotic/autophagic cell death of many cancer cells/CSCs, it appears to induce autophagic survival/quiescence of a subset of DCLK1 +ve CSCs (Figs 2A,2B,5Aii and 6A), representing a novel aspect of our findings.…”

Section: Discussionmentioning

confidence: 99%

“…After 24–48h of treatment, cells were processed for measuring viability/proliferation/apoptosis/autophagy by published methods (8,17,18), as detailed in supplementary-methods(B). Briefly, Viability/proliferation of cells was measured by trypan blue exclusion test and MTT assay, respectively, as described (8).…”

Section: Methodsmentioning

confidence: 99%

“…Autophagy represents a double-edged sword which causes either cell death or survival of cells (16). Majority of the studies suggest that curcumin-induced autophagy is a pro-death signal (13,17,18). However, curcumin-induced autophagy also allows tumor initiating cells to survive and either differentiate (19), or become senescent/quiescent (20,21).…”

Section: Introductionmentioning

confidence: 99%

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Curcumin Promotes Autophagic Survival of a Subset of Colon Cancer Stem Cells, Which Are Ablated by DCLK1-siRNA

et al. 2014

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Curcumin is known to induce apoptosis of cancer cells by different mechanisms, but its effects on cancer stem-like cells have been less investigated. Here we report that curcumin promotes the survival of DCLK1-positive colon cancer stem-like cells (CSC), potentially confounding application of its anticancer properties. At optimal concentrations, curcumin greatly reduced expression levels of stem cell markers (DCLK1/CD44/ALDHA1/Lgr5/Nanog) in 3D spheroid cultures and tumor xenografts derived from colon cancer cells. However, curcumin unexpectedly induced proliferation and autophagic survival of a subset of DCLK1-positive CSCs. Spheroid cultures were disintegrated by curcumin in vitro but re-grew within 30–40 days of treatment, suggesting a survival benefit from autophagy, permitting long-term persistence of CRC. Notably, RNAi-mediated silencing of DCLK1 triggered apoptotic cell death of colon cancer cells in vitro and in vivo, and abolished CRC survival in response to curcumin; combination of DCLK1-siRNA and curcumin dramatically reversed CSC phenotype, contributing to attenuation of the growth of spheroid cultures and tumor xenografts. Taken together, our findings confirm a role of DCLK1 in colon cancer stem cells and highlight DCLK1 as a target to enhance antitumor properties of curcumin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Curcumin Promotes Autophagic Survival of a Subset of Colon Cancer Stem Cells, Which Are Ablated by DCLK1-siRNA

et al. 2014

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“…Recently, curcumin (Yu et al, 2011;Li et al, 2013;Zhou et al, 2013;Yin et al, 2013) and triptolide (Kim et al, 2010;Liu et al, 2012;Wen et al, 2012) are able to potently inhibit the growth of human cancer cells in vitro and prevents tumor growth in vivo via inhibiting cell proliferation and inducing apoptosis. However, both of curcumin and triptolide possess side effects in high concentration (Banjerdpongchai et al, 2005;Clawson et al, 2010;Antonoff et al, 2010;Li et al, 2010;Borja-Cacho et al, 2010;Shakibaei et al, 2013;Du et al, 2013;Jiang et al, 2013).…”

Section: Combined Effects Of Curcumin and Triptolide On An Ovarian Camentioning

confidence: 99%

Combined Effects of Curcumin and Triptolide on an Ovarian Cancer Cell Line

Cai

Lin²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.Keywords: Curcumin -triptolide -ovarian cancer cell line -cytotoxicity RESEARCH ARTICLE Combined Effects of Curcumin and Triptolide on an Ovarian Cancer Cell LineYing-Ying Cai*, Wei-Ping Lin, Ai-Ping Li, Jian-Yang Xu Pacak et al., 2012;Hsu et al.,2013;Tan et al., 2013;Huang et al., 2013). Recently, curcumin (Yu et al., 2011;Li et al., 2013;Zhou et al., 2013;Yin et al., 2013) and triptolide (Kim et al., 2010;Liu et al., 2012;Wen et al., 2012) are able to potently inhibit the growth of human cancer cells in vitro and prevents tumor growth in vivo via inhibiting cell proliferation and inducing apoptosis. However, both of curcumin and triptolide possess side effects in high concentration (Banjerdpongchai et al., 2005;Clawson et al., 2010;Antonoff et al., 2010;Li et al., 2010;Borja-Cacho et al., 2010;Shakibaei et al., 2013;Du et al., 2013;Jiang et al., 2013).To decrease the side effects and enhance the efficacy of traditional Chinese medicine (TCM) prescriptions, combinations of different TCM herbs is alternative strategy for cancer therapy. The present study was aimed to analysis the combined effect of curcumin and triptolide on ovarian cancer cell lines in vitro. Materials and Methods Reagents and cell cultureCurcumin was purchased from the Sigma-Aldrich Trading Co, Ltd (Shanghai, China); it was dissolved in DMSO to obtain 1 mM stock solution and kept at -20 °C until use, and then diluted in medium to different concentrations. Triptolide (purity > 99.0%, Institute of Human ovarian cancer OVAR3, SKOV3, HO-8910 and A2780 cell lines were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA). Cells were cultured in Dulbecco's Modified Eagle's medium (DMEM) supplemented with 10 % fetal bovine serum (F...

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Targeting autophagy using natural compounds for cancer prevention and therapy

Deng

Shanmugam

Kumar

et al. 2019

Cancer

268

188

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Autophagy, also known as macroautophagy, is a tightly regulated process involved in the stress responses, such as starvation. It is a vacuolar, lysosomal pathway for the degradation of damaged proteins and organelles in eukaryotic cells. Autophagy also plays a key role in various tissue processes and immune responses and in the regulation of inflammation. Over the past decade, three levels of autophagy regulation have been identified in mammalian cells: 1) signaling, 2) autophagosome formation, and 3) autophagosome maturation and lysosomal degradation. Any deregulation of the autophagy processes can lead to the development of diverse chronic diseases, such as diabetes, obesity, cardiovascular disease, neurodegenerative disease, and malignancies. However, the potential role of autophagy in cancer is rather complex and has been associated with both the induction and the inhibition of neoplasia. Several synthetic autophagy modulators have been identified as promising candidates for cancer therapy. In addition, diverse phytochemicals derived from natural sources, such as curcumin, ursolic acid, resveratrol, thymoquinone, and γ‐tocotrienol, also have attracted attention as promising autophagy modulators with minimal side effects. In this review, the authors discuss the importance of autophagy regulators and various natural compounds that induce and/or inhibit autophagy in the prevention and therapy of cancer.

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Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells

Abstract: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

Cited by 43 publications

References 24 publications

Curcumin Promotes Autophagic Survival of a Subset of Colon Cancer Stem Cells, Which Are Ablated by DCLK1-siRNA

Curcumin Promotes Autophagic Survival of a Subset of Colon Cancer Stem Cells, Which Are Ablated by DCLK1-siRNA

Combined Effects of Curcumin and Triptolide on an Ovarian Cancer Cell Line

Targeting autophagy using natural compounds for cancer prevention and therapy

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