Resveratrol induces cell death in cervical cancer cells through apoptosis and autophagy

García-Zepeda, Sihomara Patricia; García‐Villa, Enrique; Díaz-Chávez, José; Hernández-Pando, Rogelio; Gariglio, Patricio

doi:10.1097/cej.0b013e328360345f

Cited by 102 publications

(72 citation statements)

References 31 publications

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“…A body of evidence indicates that resveratrol has inhibitory effects on many types of malignancies including the squamous cell carcinomas and adenocarcinomas of uterus cervical cancers [28,29]. Nevertheless, the molecular mechanism underlying the effects of resveratrol on cervical cancers remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells

Peng

Yang

et al. 2014

Genes Cancer

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Cervical cancers/CCs are one of the commonest malignancies and the second leading cause of cancer-related death in women. Resveratrol inhibits CC cell growth but its molecular target(s) remains unclear. Since the signaling pathways mediated by STAT3, Notch1 and Wnt2 play beneficial roles in CC formation and progression, the effects of resveratrol on them in cervical adenocarcinoma (HeLa) and squamous cell carcinoma (SiHa) cells were analyzed. The biological significances of the above signaling for HeLa and SiHa cells were evaluated by treating the cells with STAT3, Wnt or Notch selective inhibitors. The frequencies of STAT3, Notch and Wnt activations in 68 cases of CC specimens and 38 non-cancerous cervical epithelia were examined by tissue microarray-based immunohistochemical staining. The results revealed that HeLa and SiHa cells treated by 100μM resveratrol showed extensive apoptosis, accompanied with suppression of STAT3, Notch and Wnt activations. Growth inhibition and apoptosis were found in HeLa and SiHa populations treated by AG490, a STAT3/JAK3 inhibitor but not the ones treated by Notch inhibitor L-685,458 or by Wnt inhibitor XAV-939. Immunohistochemical staining performed on the tissue microarrays showed that the frequencies of Notch1, Notch2, Hes1, Wnt2, Wnt5a and p-STAT3 detection as well as β-catenin nuclear translocation in CC samples were significantly higher than that of noncancerous group (p<0.01), while the expression rate of PIAS3 was remarkably low in cancer samples (p<0.01). Our results thus demonstrate that STAT3, Wnt and Notch signaling are frequently co-activated in human CC cells and specimens and resveratrol can concurrently inhibit those signaling activations and meanwhile lead cervical squamous cell carcinoma and adenocarcinoma cells to growth arrest and apoptosis. STAT3 signaling is more critical for CC cells and is the major target of resveratrol because selective inhibition of STAT3 rather than Wnt or Notch activation commits SiHa and HeLa cells to apoptosis.

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Section: Discussionmentioning

confidence: 99%

Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells

Peng

Yang

et al. 2014

Genes Cancer

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“…A large body of evidence has shown that Resveratrol has antiviral, antioxidant and anti-inflammatory actions, and may help prevent the development of certain cancers and cardiovascular diseases [19,22]. Resveratrol at a dosage of 146 mg/kg/day in rats may attenuate pathology left ventricular hypertrophy via inhibiting NFAT-dependent transcription [17].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, more and more studies uncover that Resveratrol has anticancer actions on a variety of cancers [19]. Resveratrol was shown to induce cell death in cervical cancer cells through apoptosis and autophagy [19]. An antitumor activity of Resveratrol was identified in human colorectal cancer cell lines through calorie-restriction pathway [20].…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis

Yin

Zhao

Feng

et al. 2015

Cell Physiol Biochem

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Background/Aims: Low ambient temperature is an important risk factor for cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In this study, we aim to investigate if Resveratrol may inhibit cold exposure-induced cardiac hypertrophy in mice, and if so to clarify its molecular mechanism. Methods: Adult male mice were randomly assigned to Control group (kept at room temperature), Cold group (kept at low air temperature range from 3°C to 5°C) and Resveratrol treatment group (100mg/kg/day) for eight weeks. HE staining, Masson staining and Transmission electron microscopy were employed to detect cardiac structure, fibrosis and myocardial ultrastructure, respectively. Echocardiogram was used to measure myocardial functions. Western blot was used to detect the expression of MAPK pathway and apoptotic proteins. TUENL assay was performed to evaluate cardiomyocyte apoptosis. qRT-PCR was employed to measure the mRNA level. Results: Cold-treated mice showed a higher heart/body weight ratio and heart weight/tibia length ratio compared with control mice, and Resveratrol treatment may suppress these changes in cold-treated mice. Myocardial cross-section area and cardiac collagen volume were larger in cold group than control group, which also can be attenuated by Resveratrol treatment. Also, Resveratrol improved the ultrastructure damage of myocardium such as myofibril disarray in cold group. Echocardiogram measurement showed that EF and FS values in cold group declined apparently as compared to control group, and Resveratrol may improve the reduction of heart functions. The expression of p-JNK, p-p38 and p-ERK relative to total JNK, p38 and ERK in cold group was not altered in cold group and Resveratrol group as compared to control group. Cold-treated mouse hearts also showed the upregulation of hypertrophy-related miRNA-miR-328 but not miR-23a, and Resveratrol treatment can inhibit the increase of miR-328. Finally, Resveratrol treatment also may suppress apoptosis of myocardium in cold-treated mouse hearts via inhibiting Bax and caspase-3 activation. Conclusion: In summary, low ambient temperature can cause enlarged heart, ultrastructure damage of myocardium and weakened functions, and Resveratrol treatment effectively suppressed these changes at least partially via inhibiting cardiomyocyte apoptosis.

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“…1). The recent extensive studies on the resveratrol and its derivatives revealed that they have antioxidant, 5 antimutagenic, 6 antiinflammatory, 7 antidiabetic, 8 cardiovascular protective, 9 and anticancer 10 properties. It has been believed that the majority of the biological functions of resveratrol has been attributed to its antioxidant activity.…”

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confidence: 99%

Syntheses of Resveratrol Analogues and Evaluation of Their Antioxidant Activity

Kim¹,

Jung²,

Moon³

et al. 2014

Bulletin of the Korean Chemical Society

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Reactive oxygen species (ROS) referring free radicals with oxygen molecules are produced in the body as byproducts during the normal metabolic process which generates energy by the oxidation of carbohydrates, fats, and proteins. Free radicals such as superoxide anion radicals (O 2 •¯), hydroxyl radicals (•OH) and non-free radical species such as hydrogen peroxide (H 2 O 2 ) and singlet oxygen ( 1 O 2 ) are considered as ROS.1 These ROS not only oxidize membrane lipids but damage nucleic acids, proteins and carbohydrates leading to mutations.2 If ROS are not scavenged by antioxidants, they could be involved in ageing and various diseases related to oxidative stress.

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Resveratrol induces cell death in cervical cancer cells through apoptosis and autophagy

Cited by 102 publications

References 31 publications

Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells

Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells

Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis

Syntheses of Resveratrol Analogues and Evaluation of Their Antioxidant Activity

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