Apoptosis, Free Radicals and Antioxidant Defense in Antitumor Therapy

Kulbacka, Julita; Saczko, Jolanta; Chwiłkowska, Agnieszka; Choromańska, Anna; Skołucka, Nina

doi:10.5772/50357

Cited by 16 publications

(17 citation statements)

References 222 publications

(236 reference statements)

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“…However, in A35-treated cancer cells, although apoptosis appeared, the mitochondria apoptosis pathway was not activated, which indicated the distinct mechanism from its parental core berberine in apoptosis induction. Usually except mitochondria caspase9, some non-mitochondrial caspases such as caspase-2, caspase-8 and caspase10 also play key role in activating effector caspase-7 [ 52 ], thus we speculate A35-induced caspase-7 activation and subsequent apoptosis might be a result of activation of non-mitochondrial caspases. This also arouses our interest and in the following study we will continue working on this issue.…”

Section: Discussionmentioning

confidence: 99%

The dual topoisomerase inhibitor A35 preferentially and specially targets topoisomerase 2α by enhancing pre-strand and post-strand cleavage and inhibiting DNA religation

Zhao

Jiang

et al. 2015

Oncotarget

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DNA topoisomerases play a key role in tumor proliferation. Chemotherapeutics targeting topoisomerases have been widely used in clinical oncology, but resistance and side effects, particularly cardiotoxicity, usually limit their application. Clinical data show that a decrease in topoisomerase (top) levels is the primary factor responsible for resistance, but in cells there is compensatory effect between the levels of top1 and top2α. Here, we validated cyclizing-berberine A35, which is a dual top inhibitor and preferentially targets top2α. The impact on the top2α catalytic cycle indicated that A35 could intercalate into DNA but did not interfere with DNA-top binding and top2α ATPase activity. A35 could facilitate DNA-top2α cleavage complex formation by enhancing pre-strand and post-strand cleavage and inhibiting religation, suggesting this compound can be a topoisomerase poison and had a district mechanism from other topoisomerase inhibitors. TARDIS and comet assays showed that A35 could induce cell DNA breakage and DNA-top complexes but had no effect on the cardiac toxicity inducer top2β. Silencing top1 augmented DNA break and silencing top2α decreased DNA break. Further validation in H9c2 cardiac cells showed A35 did not disturb cell proliferation and mitochondrial membrane potency. Additionally, an assay with nude mice further demonstrated A35 did not damage the heart. Our work identifies A35 as a novel skeleton compound dually inhibits topoisomerases, and predominantly and specially targets top2α by interfering with all cleavage steps and its no cardiac toxicity was verified by cardiac cells and mice heart. A35 could be a novel and effective targeting topoisomerase agent.

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Section: Discussionmentioning

confidence: 99%

The dual topoisomerase inhibitor A35 preferentially and specially targets topoisomerase 2α by enhancing pre-strand and post-strand cleavage and inhibiting DNA religation

Zhao

Jiang

et al. 2015

Oncotarget

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“…In order to overcome the protective effects of SOD, combinations of SOD inhibitors such as; potassium cyanide, chloroform-ethanol, H2O2 and NaN3, administered together with PDT might increase the efficiency of the anticancer treatment. 89,90 Modified PDT techniques have been developed to overcome reduced oxygen levels, which ultimately reduces the efficacy of PDT in tumour microenvironments, which houses CSCs. Usacheva et al 91 increased production of ROS using surfactant–polymer NP which also proved effective at eliminating CSCs.…”

Section: Overcoming Resistance To Pdt Of Cscsmentioning

confidence: 99%

Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells

2017

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Colorectal cancer is commonly treated by tumour resection, as chemotherapy and radiation have proven to be less effective, especially if the tumour has metastasized. Resistance to therapies occurs in almost all patients with colorectal cancer, especially in those with metastatic tumours. Cancer stem cells have the ability to self-renew, and their slow rate of cycling enhances resistance to treatment and increases the likelihood of tumour recurrence. Most metastatic tumours are unable to be surgically removed, thus creating a need for treatment modalities that target cancers directly and destroy cancer stem cells. Photodynamic therapy involves a photosensitizer that when exposed to a light source of a particular wavelength becomes excited and produces a form of oxygen that kills cancer cells. Photodynamic therapy is currently being investigated as a treatment modality for colorectal cancer, and new studies are exploring enhancing photodynamic therapy efficacy with the aid of drug carriers and immune conjugates. These modifications could prove effective in targeting cancer stem cells that are thought to be resistant to photodynamic therapy. In order for photodynamic therapy to be an effective treatment in colorectal cancer, it requires treatment of both primary tumours and the metastatic secondary disease that is caused by colon cancer stem cells. This review focuses on current photodynamic therapy treatments available for colorectal cancer and highlights proposed actively targeted photosynthetic drug uptake mechanisms specifically mediated towards colon cancer stem cells, as well as identify the gaps in research which need to be investigated in order to develop a combinative targeted photodynamic therapy regime that can effectively control colorectal cancer primary and metastatic tumour growth by eliminating colon cancer stem cells.

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“…For the flavonoids and their derivatives, those with the strongest antioxidant potential include delphinine, epicatechin, kaempferol, quercetin, and luteolin. Quercetin, the most abundant dietary flavonol, is a potent antioxidant because it has all structural features for free radical scavenging activity [ 40 , 41 ]. It has been reported that catechins interact with the cell wall and membrane of bacterial cells [ 42 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Biological Properties of Two Medicinal Extracts of the Tehuacan‐Cuicatlan Valley

Martinez-Elizalde

Rodríguez-Monroy²,

Flores-Ortíz³

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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In the Valley of Tehuacan-Cuicatlan, Cyrtocarpa procera and Bursera morelensis are located and are used in traditional medicine. In this research, several biological properties were evaluated. The methanol extracts of C. procera (MeCp) and B. morelensis (MeBm) were obtained by maceration. The antibacterial activities of the extracts were evaluated by the Kirby–Baüer disc-diffusion method. The wound healing activity was evaluated by histopathological analysis. Both extracts had a bacteriostatic effect in the Staphylococcus aureus (MeCp MIC = 0.25 mg/mL and MeBm MIC = 1 mg/mL) and the Vibrio cholerae (MeCp MIC = 1 mg/mL and MeBm MIC = 4 mg/mL). Both extracts demonstrated a wound healing efficacy similar to the reference standard (Recoveron). They also showed a high antioxidant capacity (MeCp SC50 = 5.75 μg/mL and MeBm SC50 = 4.27 μg/mL). These results are related to the concentration of phenols (MeCp = 166 and MeBm = 236.6 mg GAe/g) and flavonoids of MeCp = 16 and MeBm = 22 μg Qe/g. Both extracts, acting in a similar way in microorganisms that cause infection thanks to their antioxidant activity, favor the healing of wounds. This is the first study in which the biological properties of these two species are compared.

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Apoptosis, Free Radicals and Antioxidant Defense in Antitumor Therapy

Cited by 16 publications

References 222 publications

The dual topoisomerase inhibitor A35 preferentially and specially targets topoisomerase 2α by enhancing pre-strand and post-strand cleavage and inhibiting DNA religation

The dual topoisomerase inhibitor A35 preferentially and specially targets topoisomerase 2α by enhancing pre-strand and post-strand cleavage and inhibiting DNA religation

Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells

Comparison of Biological Properties of Two Medicinal Extracts of the Tehuacan‐Cuicatlan Valley

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