Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells

Jeon, Ju‐Hong

doi:10.3892/ijo.2011.1318

Cited by 25 publications

(20 citation statements)

References 31 publications

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“…Antioxidants are extensively studied for their ability to prevent or treat cancer in humans (90). Research has so far showed that monoterpenes such as myrtenal, vallesiachotamine, geraniol, terpinen-4-ol, and linalool exhibit anticancerogenic properties in different experimental models (liver, melanoma, prostate, and non-small cell lung and breast cancers) (91)(92)(93)(94)(95). TPO was also suggested to have an important in vitro antitumour effect against K562 human leukemic (70), breast, and cervical cancers (71) and Ehrlich ascites carcinoma cells (96).…”

Section: Discussionmentioning

confidence: 99%

Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

Aydın

Türkez

Taşdemir

2013

Archives of Industrial Hygiene and Toxicology

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Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO's antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(-1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1) it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

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Section: Discussionmentioning

confidence: 99%

Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

Aydın

Türkez

Taşdemir

2013

Archives of Industrial Hygiene and Toxicology

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“…In contrast to TRPML1, TRPML3 exhibits more limited tissue distribution and is mostly localized to early as well as late endosomes/lysosomes and less to the PM [59, 69]. Recent studies by Kim et al, 2009 showed that overexpression of TRPML3 leads to increased autophagy in HeLa cells and that TRPML3 channels are engaged to autophagosomes upon induction of autophagy [70]. Furthermore, expression of dominant negative mutant TRPML3 (D458K) or knockdown of endogenous TRPML3 by siRNA reduces autophagy.…”

Section: Trp Channels and Ca2+ Signalingmentioning

confidence: 99%

Functional role of TRP channels in modulating ER stress and Autophagy

et al. 2016

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Intracellular calcium (Ca2+) levels play a vital role in regulating cellular fate. The coordination and interrelation among the cellular organelles, mainly the intracellular Ca2+ stores in endoplasmic reticulum (ER), are crucial in maintaining cytosolic Ca2+ levels and in general cellular homeostasis. Moreover, maintaining Ca2+ homeostasis is essential for regulating diverse and sometimes opposing processes such as cell survival and cell death in disease conditions such as, neurodegeneration, cancer and aging. Ca2+ is able to regulate opposing functions by either regulating the cellular “self-eating” phenomenon of autophagy to promote cell survival or by regulating the programmed cell death process of apoptosis. Autophagy is also important for cell survival especially after induction of ER stress and association between ER stress and autophagy may have relevance to numerous diseases. Moreover, a multitude of evidence is emerging that the functional regulation of TRP channels, their unique localization, and their interaction with other Ca2+-sensing elements define these diverse regulatory pathways. It is this unique function which allows individual TRP channels to contribute differently in the regulation of cell fate and, in turn, determines the precise effect of modulating Ca2+ signaling via the particular channel. Thus, in this review we have focused on the aspects of TRP channel localization and function (Ca2+ signaling) that affects the ER stress and autophagic process.

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“…The natural compound geraniol is an anti-cancer agent, which suppresses the growth of various tumors, such as prostate cancer [ 28 ], colon cancer [ 29 ], lung cancer [ 30 ], hepatic cancer [ 31 ], pancreatic cancer [ 32 ] as well as oral and skin cancer [ 15 , 33 , 34 ]. By now, this anti-tumor activity has been mainly attributed to direct geraniol effects on tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling

et al. 2015

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Geraniol exerts several direct pharmacological effects on tumor cells and, thus, has been suggested as a promising anti-cancer compound. Because vascularization is a major precondition for tumor growth, we analyzed in this study the anti-angiogenic action of geraniol. In vitro, geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that geraniol downregulates proliferating cell nuclear antigen (PCNA) and upregulates cleaved caspase-3 (Casp-3) expression in eEND2 cells. Moreover, geraniol blocked vascular endothelial growth factor (VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition, geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo, geraniol inhibited the vascularization of CT26 tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced VEGFR-2 expression within geraniol-treated tumors. Taken together, these findings indicate that geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of tumors.

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Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells

Cited by 25 publications

References 31 publications

Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

Functional role of TRP channels in modulating ER stress and Autophagy

Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling

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