Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of Apoptosis

Marzo, Isabel; Brenner, Catherine; Zamzami, Naoufal; Jürgensmeier, Juliane M.; Susin, Santos A.; Vieira, Helena L.A.; Prévost, Marie-Claude; Xie, Zhihua; Matsuyama, Shigemi; Reed, John C.; Kroemer, Guido

doi:10.1126/science.281.5385.2027

Cited by 1,098 publications

(840 citation statements)

References 44 publications

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“…Fluoroquinolone antibiotics may also trigger the Bax-pathway of apoptosis or interfere directly with mitochondrial membrane proteins, as described for cyclosporin A that binds to the mitochondrial megapore (Mancini et al, 1997;Jurgensmeier et al, 1998). Thus, activation of the mitochondrial permeability transition pore by Bax with subsequent release of cytochrome c has been described (Marzo et al, 1998, Narita et al, 1998. The ability of ciprofloxacin to activate Bax was recently shown in a bladder carcinoma cell line (Aranha et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

et al. 2002

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Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substratecleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time-and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 mg ml 71 . This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated.

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Section: Discussionmentioning

confidence: 99%

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

et al. 2002

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“…When reconstituted into liposomes or into planar lipid bilayers, ANT can form nonspecific channels in response to proapoptotic agents such as atractyloside, Ca 2 þ (Brustovetsky et al, 2002), lonidamine and the HIV-1 viral protein R (Vpr) . Moreover, ANT channel formation is enhanced by Bax (Marzo et al, 1998a), and inhibited by Bcl-2 . However, mouse knockout studies led to the conclusion that ANT would not (always) be required for apoptotic MOMP (Kokoszka et al, 2004).…”

Section: Mitochondrial Membrane Permeabilization: the Central Event Omentioning

confidence: 97%

Mitochondria as therapeutic targets for cancer chemotherapy

et al. 2006

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Mitochondria are vital for cellular bioenergetics and play a central role in determining the point-of-no-return of the apoptotic process. As a consequence, mitochondria exert a dual function in carcinogenesis. Cancer-associated changes in cellular metabolism (the Warburg effect) influence mitochondrial function, and the invalidation of apoptosis is linked to an inhibition of mitochondrial outer membrane permeabilization (MOMP). On theoretical grounds, it is tempting to develop specific therapeutic interventions that target the mitochondrial Achilles' heel, rendering cancer cells metabolically unviable or subverting endogenous MOMP inhibitors. A variety of experimental therapeutic agents can directly target mitochondria, causing apoptosis induction. This applies to a heterogeneous collection of chemically unrelated compounds including positively charged a-helical peptides, agents designed to mimic the Bcl-2 homology domain 3 of Bcl-2-like proteins, ampholytic cations, metals and steroid-like compounds. Such MOMP inducers or facilitators can induce apoptosis by themselves (monotherapy) or facilitate apoptosis induction in combination therapies, bypassing chemoresistance against DNA-damaging agents. In addition, it is possible to design molecules that neutralize inhibitor of apoptosis proteins (IAPs) or heat shock protein 70 (HSP70). Such IAP or HSP70 inhibitors can mimic the action of mitochondrion-derived mediators (Smac/DIABLO, that is, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with a low isoelectric point, in the case of IAPs; AIF, that is apoptosis-inducing factor, in the case of HSP70) and exert potent chemosensitizing effects.

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“…BAX was shown to directly interact with ANT both by coimmunoprecipitation and by the yeast two hybrid system [61]. Moreover, this interaction was shown to be important for optimal opening of the PTP in response to atractyloside, both in isolated mitochondria and by in-vitro experiments using reconstituted ANT and BAX [62].…”

Section: Ant Bax and Tbidmentioning

confidence: 99%

Mitochondrial carriers and pores: Key regulators of the mitochondrial apoptotic program?

2007

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Mitochondria play a pivotal role in the process of apoptosis. Alterations in mitochondrial structure and function during apoptosis are regulated by proteins of the BCL-2 family, however their exact mechanism of action is largely unknown. Mitochondrial carriers and pores play an essential role in maintaining the normal function of mitochondria, and BCL-2 family members were shown to interact with several mitochondrial carriers/pores and to affect their function. This review focuses on the involvement of several of these mitochondrial carriers/pores in the regulation of the mitochondrial death pathway.

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Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of Apoptosis

Cited by 1,098 publications

References 44 publications

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

Mitochondria as therapeutic targets for cancer chemotherapy

Mitochondrial carriers and pores: Key regulators of the mitochondrial apoptotic program?

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