Mitochondria-dependent apoptosis induced by a novel amphipathic photochemotherapeutic agent ZnPcS2P2 in HL60 cells1

Huang, Huifang; Chen, Yuanzhong; Wu, Yong

doi:10.1111/j.1745-7254.2005.00160.x

Cited by 15 publications

(8 citation statements)

References 30 publications

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“…Similar results were also described recently for another photosensitizer, disulfonated diphthalimidomethyl phthalocyanine zinc (ZnPcS 2 P 2 ) [23]. Additionally, we observed that the irradiated riboflavin leads to leukaemia cell proliferation inhibition as shown by the activation of p21 and downregulation of PCNA.…”

Section: Discussionsupporting

confidence: 89%

A promising action of riboflavin as a mediator of leukaemia cell death

et al. 2006

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Besides having a pivotal biological function as a component of coenzymes, riboflavin appears a promissing antitumoral agent, but the underlying molecular mechanism remains unclear. In this work, we demonstrate that irradiated riboflavin, when applied at microM concentrations, induces an orderly sequence of signaling events finally leading to leukemia cell death. The molecular mechanism involved is dependent on the activation of caspase 8 caused by overexpression of Fas and FasL and also on mitochondrial amplification mechanisms, involving the stimulation of ceramide production by sphingomyelinase and ceramide synthase. The activation of this cascade led to an inhibition of mitogen activated protein kinases: JNK, MEK and ERK and survival mediators (PKB and IAP1), upregulation of the proapoptotic Bcl2 member Bax and downregulation of cell cycle progression regulators. Importantly, induction of apoptosis by irradiated riboflavin was leukaemia cell specific, as normal human lymphocytes did not respond to the compound with cell death. Our data indicate that riboflavin selectively activates Fas cascade and also constitutes a death receptor-engaged drug without harmful side effects in normal cells, bolstering the case for using this compound as a novel avenue for combating cancerous disease.

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Section: Discussionsupporting

confidence: 89%

A promising action of riboflavin as a mediator of leukaemia cell death

et al. 2006

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“…The drop in the intermembrane potential mainly detected in the perinuclear mitochondria can be related to the intracellular localization of RB, being predominantly present in the perinuclear cytoplasmic region. The structural alterations are consistent with the induction of apoptotic cell death; in fact, the ballooning of mitochondria, with disruption of the cristae and internal organelle structure, we found by Xuorescence and electron microscopy at 48 h p-t was also described by Luchetti et al (2006) for apoptotic U937 promonocytic leukemia cells exposed to UV-B, and by Huang et al (2005) for HL60 cells upon photosensitization. Similarly swollen mitochondria were described by Shen et al (2002) in apoptotic esophageal carci- Fig.…”

Section: Discussionsupporting

confidence: 75%

Enzyme-assisted photosensitization with rose Bengal acetate induces structural and functional alteration of mitochondria in HeLa cells

Bottone

Soldani

Fraschini

et al. 2006

Histochem Cell Biol

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Rose Bengal acetate (RB-Ac) can be used as a fluorogenic substrate for photosensitization of cells both in vivo and in vitro: once inside the cells, RB-Ac is converted into photoactive rose Bengal (RB) molecules which redistribute dynamically in the cytoplasm and, upon irradiation by visible green light, can damage organelles such as the endoplasmic reticulum, the Golgi apparatus, and the cytoskeleton. Recently, evidence has been provided that mitochondria may also be affected. The aims of the present study were to describe RB-induced photodamage of mitochondria in single HeLa cells and to define, on a quantitative basis, the effects of photosensitization on their morphofunctional features. HeLa cell cultures were exposed to 10(-5) M RB-Ac for 60 min and then irradiated with a light emitting diode at 530 nm (total light dose, 1.6 J/cm2). After irradiation, the cells were transferred to a drug-free complete medium and allowed to grow for 24-72 h. Using conventional and confocal fluorescence microscopy, transmission electron microscopy, and flow cytometry, we demonstrate that, in photosensitized cells, mitochondria undergo structural and functional alterations which can lead cells to apoptosis. Interestingly, in our system some cells were able to survive 72 h post-treatment and to recover, exhibiting the same mitochondrial structure, distribution and inner membrane potential as those in untreated controls. Taking into account that the photoactive molecules redistribute dynamically inside the cell upon RB-Ac administration, it may be hypothesized that cells can be differently affected by irradiation, depending on the relative amount and organelle location of the photosensitizer.

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“…Zinc can sensitize cancer cells for physical agents; disulfonated diphthalimidomethyl phthalocyanine zinc (ZnPcS 2 P 2 ) has been used to induce mitochondria‐dependent apoptosis in K562 and HL60 cells as a novel amphipathic photosensitizer (Huang et al., 2005a, b). Exposure to H 2 O 2 increased DNA fragmentation in K562 cells, preincubated with ZnSO 4 , indicating that zinc sensitized cancer cells to genotoxic agents in contrary to normal cells.…”

Section: Discussionmentioning

confidence: 99%

Zinc salts differentially modulate DNA damage in normal and cancer cells

Śliwiński

Czechowska

Kolodziejczak

et al. 2009

Cell Biology International

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Zinc plays an essential role in a wide range of cellular processes, including defense against free radicals and maintaining genomic stability. The presence of zinc in some proteins is fundamental for their functioning as transcription factors. Little is known about interaction between zinc and DNA, which can be important in light of reports on the role of zinc in cancer transformation and sometimes contradictory character of these reports. In the present study we studied cyto- and genotoxicity of zinc sulfate (ZnSO(4)) in normal human lymphocytes and human myelogenous leukemia K562 cancer cells in the presence of zinc and hydrogen peroxide (H(2)O(2)). Zinc at concentrations from the range 10-1000 microM decreased the viability of cancer cells and this effect, especially for low concentrations of the element, was much more pronounced than in normal cells. Zinc did not induce DNA damage in normal cells, but did so in cancer cells. We observed a key difference between the action of zinc in normal and cancer cells in the presence of H(2)O(2), since the element exerted a protective effect against cyto- and geno-toxic action of H(2)O(2) in the former, whereas it increased such action in the latter. Zinc inhibited the repair of DNA damage induced by H(2)O(2) in cancer cells. The results suggest that zinc may protect normal cells against DNA-damaging action and increase this action in cancer cells, which indicates the dual action of this element in dependency of target cells and can be useful in cancer therapy.

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Mitochondria-dependent apoptosis induced by a novel amphipathic photochemotherapeutic agent ZnPcS2P2 in HL60 cells1

Cited by 15 publications

References 30 publications

A promising action of riboflavin as a mediator of leukaemia cell death

A promising action of riboflavin as a mediator of leukaemia cell death

Enzyme-assisted photosensitization with rose Bengal acetate induces structural and functional alteration of mitochondria in HeLa cells

Zinc salts differentially modulate DNA damage in normal and cancer cells

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