Effect of kinetin riboside on proapoptotic activities in human cancer and normal cell lines

Orlicka-Płocka, Marta; Gurda, Dorota; Fedoruk-Wyszomirska, Agnieszka; Barciszewski, Jan; Wyszko, Eliza

doi:10.1016/j.nbt.2016.06.1303

Cited by 2 publications

(3 citation statements)

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“…It is known that KR can disrupt the energy balance in cells through phosphorylation by ADK, which is crucial for KR toxicity [8,21,51,52]. We also showed that in response to KR treatment in galactose medium, HepG2 cells undergo extensive apoptosis, which is likely a direct consequence of the rapid decrease in the cellular ATP level (Fig.…”

Section: Discussionsupporting

confidence: 56%

Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside

et al. 2020

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Small-molecule compound-based therapies have provided new insights into cancer treatment against mitochondrial impairment. N6-furfuryladenosine (kinetin riboside, KR) is a purine derivative and an anticancer agent that selectively affects the molecular pathways crucial for cell growth and apoptosis by interfering with mitochondrial functions and thus might be a potential mitotoxicant. Metabolism of cancer cells is predominantly based on the Crabtree effect that relies on glucose-induced inhibition of cell respiration and thus on oxidative phosphorylation (OXPHOS), which supports the survival of cancer cells in metabolic stress conditions. The simplest way to circumvent this phenomenon is to replace glucose with galactose in the culture environment. Consequently, cells become more sensitive to mitochondrial perturbations caused by mitotoxicants. In the present study, we evaluated several cellular parameters and investigated the effect of KR on mitochondrial functions in HepG2 cells forced to rely mainly on OXPHOS. We showed that KR in the galactose environment is a more potent apoptosis-inducing agent. KR decreases the mitochondrial membrane potential, reduces glutathione level, depletes cellular ATP, and induces reactive oxygen species (ROS) production in the OXPHOS state, leading to the loss of cell viability. Taken together, these results demonstrate that KR directly acts on the mitochondria to limit their function and that the sensitivity of cells is dependent on their ability to cope with energetic stress.

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Section: Discussionsupporting

confidence: 56%

Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside

et al. 2020

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“…Natural small compounds are also considered to selectively influence various stages of intracellular molecular pathways that are crucial for proliferation and cell death [63]. It is confirmed that purine derivatives, belonging to the group of small compounds, could be potentially utilized to enhance the metabolic vulnerability of cancer cells, and these compounds have been shown to affect mitochondrial impairment [12,64] and induce oxidative stress [12].…”

Section: Discussionmentioning

confidence: 98%

“…We confirmed that these two adenosine analogues induce toxicity in T98G cells, inhibit cell proliferation, and initiate cell apoptosis in a dose-dependent manner (Figure 6D-G) through the salvage pathway of purine metabolism (Figure 6A). However, the effect on cellular proliferation was entirely averted when the cells were treated with 5-iodotubericidin, an inhibitor of ADK (Figure 6F,G); this indicated that the intracellular phosphorylation of the majority of purines is necessary to exert its cytotoxicity (Figure 6A,B) [63,79,80].…”

Section: Discussionmentioning

confidence: 99%

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

et al. 2021

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Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

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Effect of kinetin riboside on proapoptotic activities in human cancer and normal cell lines

Cited by 2 publications

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Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside

Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

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