{'fraction_non_alphanumeric': 0.046073977936404935, 'fraction_numerical': 0.012978585334198572, 'mean_word_length': 4.908045977011494, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Transforming Growth Factor-β-Mediated Apoptosis in the Ramos B-Lymphoma Cell Line Is Accompanied by Caspase Activation and Bcl-XLDownregulation

Abstract Upon transforming growth factor-β (TGF-β) treatment, Ramos cells, a B-cell lymphoma cell line, undergo apoptosis, as measured by annexin V labeling, DNA fragmentation, and propidium iodide staining. Apoptosis could be observed by 24 h after TGF-β exposure and occurred before the development of a significant blockage of cell cycle progression. TGF-β-mediated apoptosis was also accompanied by a strong induction of caspase-3 subfamily activity. Incubation of cells with the caspase inhibitor Z-VAD.FMK at 20 μM, but not at 10 μM, prevented TGF-β-induced apoptosis from occurring. By comparison, caspase-3 subfamily activity was 87% inhibited at 10 μM Z-VAD.FMK and completely inhibited at 20 μM. Because of TGF-β's well-established role of regulating gene transcription, the mRNA levels for proteins associated with apoptosis (Fas- and Fas-associated proteins, Bcl-2 family members, IAP proteins, and IκB) were also studied. After 24 h of TGF-β treatment, the most significant mRNA changes occurred with Bcl-X L (twofold decrease) and Bik (twofold increase). TGF-β treatment also resulted after 48 h in a fivefold decrease in Bcl-X L protein levels, based on immunoblotting analysis. Therefore, TGF-β-mediated apoptosis involves the activation of caspases. In addition, TGF-β transcriptionally regulates Bcl-2 family members, Bcl-X L and Bik, to further influence the apoptosis process.