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Acetazolamide-mediated carbonic anhydrase inhibition suppresses human peripheral blood mononuclear cell proliferation via G1/S cell cycle arrest Mustofa, Syazili; Sadikin, Mohamad; Sarmoko
Acta Biochimica Indonesiana Vol. 9 No. 1 (2026): Acta Biochimica Indonesiana
Publisher : Indonesian Society for Biochemistry and Molecular Biology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32889/actabioina.145

Abstract

Background: Carbonic anhydrase (CA) regulates intracellular CO₂/HCO₃⁻ homeostasis and supplies carboxyl donors for the sixth step of de novo purine biosynthesis. Disruption of this step is predicted to impair nucleotide pool accumulation and arrest cell cycle progression. Objective: This study investigated whether CA inhibition by acetazolamide suppresses T lymphocyte proliferation. Methods: Human peripheral blood mononuclear cells (PBMCs) were stimulated with phytohemagglutinin (PHA, 1% v/v) or interleukin-2 (IL-2, 10 ng/mL). Acetazolamide was applied at 6.25–50 μM. Cell viability, DNA synthesis, and cell cycle distribution were assessed using WST-1 assay, BrdU incorporation, and propidium iodide flow cytometry, respectively. Results: Acetazolamide reduced PBMC viability and DNA synthesis dose-dependently in both PHA- and IL-2-stimulated cultures (p < 0.05). IL-2-stimulated cells showed greater sensitivity, with significant inhibition at 12.5 μM versus 25 μM for PHA-stimulated cells. Flow cytometry revealed G1/S arrest in all treated groups: S phase decreased from 8.52% to 3.82% (PHA) and from 1.27% to 0% (IL-2) at 50 μM, with G2/M uniformly suppressed to ≤0.57%. Conclusion: Acetazolamide suppresses PBMC proliferation through G1/S arrest, consistent with CA inhibition depleting CO₂/HCO₃⁻-dependent carboxyl donors required for de novo purine synthesis.
Co-Authors . Anindyajati Abdul Karim, Dewi Damayanti Achmad Baihaqi Ulma Adam Hermawan Adinda Salsabila Aditya Fitriasari Aditya Fitriasari Afif Hariawan Pratama Agung Endro Nugroho Agustin, Lanita Alsadila, Kalista Anandar, Salsabila Fauziah Anindyajati Anindyajati Anjar Hermadi Saputro Aprilia, Vika Arif Ashari Asrada, Syahdan Bama Tangguh Galih Binar Asrining Dhiani Cahyadi, Dzaky Raihan Charisa Nabirawati Sitindaon Choironi, Nur Amalia Dalili Akhmad, Atika Dika Pramita Destiani, Dika Pramita Dirga Dirga Dirga Dito Aditya Sasongko Dwi Aulia Ramdini Dyaningtyas D. P. Putri Dyaningtyas Dewi P. Putri Dyaningtyas Dewi Putri Pamungkas Edy Meiyanto Edy Meiyanto Endah Puspitasari Erna Harfiani Fadlan, Arif Fadlan, Arif Fareza, Muhamad Salman Farhan Fauzan Fauziyya, Riri Fazila, Safia Febrian, Dicky Rizky Fischellya, Dafi Hakim, Ahmad Zammi Autadan Hanif Nasiatul Baroroh HENDRI WASITO Heny Ekowati Hidayaturahmah, Rizky Ihsanti Dwi Rahayu Ingeswari, Aulya Vidiana Irna Windari, Nurul Joko Setyono Joko Setyono Khozin, Muhamad Nur Kireine Kosma Ramadhani Maharani, Putu Audi Mas Mardi Santoso Maulana Malik Mayefis, Delladari Meiyanto, Edy Mohamad Sadikin Muhamad Salman Fareza Muhammad Iqbal Muhammad Salman Fareza Muhammad Yogi Saputra Mukaromah Khoirunnisa, Sudewi Mustikaningtyas, Ika Nabila, Novrilia Atika Nabila, Sofia Zahra Nadiah, Syaadatun Nisa Yulianti Suprahman Novrilia Atika Nabila Nugraha, Yudhi Nugraheni, Zjahra Vianita Nur Adliani Nur Amalia Choironi Nur Ismiyati Nur Ismiyati Oktariza, Yasinda Pamungkas P, Dyaningtyas Dewi Pane, Esteria Christina Pangestu, Maryo Adjie Purwanata, I Gede Raditya Putra, Okta Nama Rahayyu, Annisa Maulidia Ramadhan Triyandi Ratna Asmah Susidarti Refsya Azanti Putri Rehana, Rehana Retno Wahyuningrum Retno Widiastuti Rifki Febriansah Rifki Febriansah Rispriandari, Aulia Ayu Rooswita, Putri Amelia Safei, Imam Samudra, Genta Hafied Naga Sekar Cahyo Nurani Setiyabudi, Lulu Silvia Damayanti Siregar, Fajri Marindra Sukrasno Sukrasno Syahjoko Saputra, Iwan Syazili Mustofa Tantri Liris Nareswari Tri Warsito Tri Warsito Tri Warsito Tria Putriani Triyadi Hendra Wijaya Tuti Sri Suhesti Uswatun Hasanah Vigo Atsil Nugraha Wenda Reka Pratama Wibowo, Muhammad Rizky Windari, Nurul Irna Winni Nur Auli Wisesa, Sindhu Yudhi Nugraha Yulianto, Akbar Zahra, Miralda Ziske Maritska Zusela, Titah