Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer

Zhong, Huiqin; Xiao, Mengqing; Žarković, Kamelija; Zhu, Mingyang; Sa, Rina; Lu, Jianhong; Tao, Yongzhen; Chen, Qun; Xia, Lin; Cheng, Shuqun; Waeg, Georg; Žarković, Neven; Yin, Huiyong

doi:10.1016/j.freeradbiomed.2016.10.494

Cited by 99 publications

(70 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion we may state that both PET-CT and HNE immunohistochemistry reflect cancer development related to the size of the malignant tissue, while non-malignant lung tissue in the vicinity of cancer expresses more pronounced lipid peroxidation in metastatic than in primary malignancies tending to defend itself from cancer, as was recently revealed in case of human liver cancer [44].…”

Section: Discussionsupporting

confidence: 53%

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

et al. 2017

Self Cite

View full text Add to dashboard Cite

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue.MethodsNineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts.ResultsBoth the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors.ConclusionsBoth PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer.

show abstract

Section: Discussionsupporting

confidence: 53%

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…The main metabolic alterations of the tumor cells involve increased aerobic glycolysis [42], deregulated pH [43], impaired lipid metabolism [44], increased generation of ROS [45], and compromised enzyme activities [38,46] (Figure 8). As a direct consequence, the extracellular environment becomes acidic and more favorable to inflammation [47], glutamine-driven lipid biosynthesis increases and upregulates the pathways involved in tumorigenesis initiation and metastasis [48], cardiolipin levels decrease in membranes causing impaired enzyme activities [49][50][51], mitochondria are hyperpolarised [38], and this effect correlates with the malignancy and invasiveness of cancer cells [38].…”

Section: Anticancer Effects Of Flavonoidsmentioning

confidence: 99%

Flavonoids as Anticancer Agents

et al. 2020

View full text Add to dashboard Cite

Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

show abstract

“…Since HNE is known as a second messenger of oxidative stress and in high concentrations it governs cancer cell to apoptosis, we can postulate that HNE together with the decrease of Nrf2 may have been employed in this increased chemosensitivity. In favor of this assumption are the most recent data from in vitro and clinical study that revealed a gradual decrease of cardiolipin in tissue samples of hepatocellular carcinoma in comparison to non-cancerous tissue leading to decreased oxidation of cardiolipin and consequently lesser formation of HNE which might be a possible adaptation mechanism of the cancer cells to avoid apoptosis [57].…”

Section: Cancer Therapy and Nrf2mentioning

confidence: 99%

Controversy about pharmacological modulation of Nrf2 for cancer therapy

2017

Self Cite

View full text Add to dashboard Cite

Conventional anticancer therapies such as radiotherapy and chemotherapies are associated with oxidative stress generating reactive oxygen species (ROS) and reactive aldehydes like 4-hydroxynonenal in cancer cells that govern them to die. The main mechanism activated due to exposure of the cell to these reactive species is the Nrf2-Keap1 pathway. Although Nrf2 was firstly perceived as a tumor suppressor that inhibits tumor initiation and cancer metastasis, more recent data reveal its role also as a pro-oncogenic factor. Discovery of the upregulation of Nrf2 in different types of cancer supports such undesirable pathophysiological roles of Nrf2. The upregulation of Nrf2 leads to activation of cytoprotective genes thus helping malignant cells to withstand high levels of ROS and to avoid apoptosis, eventually becoming resistant to conventional anticancer therapy. Therefore, new treatment strategies are needed for eradication of cancer and in this review, we will explore two opposing approaches for modulation of Nrf2 in cancer treatments.

show abstract

Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer

Cited by 99 publications

References 47 publications

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

Flavonoids as Anticancer Agents

Controversy about pharmacological modulation of Nrf2 for cancer therapy

Contact Info

Product

Resources

About