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   different mitotic arrest targets of chemoprevention curcumin analog 1.1 (cca-1.1) and pentagamavunone-1 (pgv-1) in leukemic k-562 cells  
   
نویسنده jenie riris istighfari ,novitasari dhania ,putri dyaningtyas dewi pamungkas ,susidarti ratna asmah ,nakamae ikuko ,yoneda-kato noriko ,kato jun-ya ,meiyanto edy
منبع pharmaceutical sciences - 2025 - دوره : 31 - شماره : 1 - صفحه:96 -105
چکیده    Background: pentagamavunone-1 (pgv-1) is a promising cytotoxic chemotherapy agent in many cancer cells. however, due to its structure, pgv-1 is unstable and easily decomposed by light or high ph, causing decreased cytotoxic effect. therefore, we developed a chemoprevention curcumin analog (cca-1.1), a novel pgv-1 derivative which demonstrated improved solubility with similar antiproliferative activities toward breast and colon cancer cells. our study intends to determine the antiproliferative effects based on the cellular and molecular mechanism of cca-1.1 and pgv-1 in leukemic cells. methods: using k-562 cells, cca-1.1 and pgv-1 were tested for the cytotoxicity effect. cell cycle analysis and ros level were assessed by flow cytometry. cells were stained with may–grünwald–giemsa and hoechst to observe the mitotic phase arrest, while the x-gal was selected to detect the senescence. the protein level of mitotic kinases (aurora a, cyclinb1, and plk1) was determined through western blot. results: cca-1.1 demonstrated an inhibitory effect on cell proliferation in k-562 cells following 96h treatment, with a gi50 value of 685 nm, akin to pgv-1 (gi50 score: 428 nm). furthermore, this effect was found to be irreversible. it was shown that 1.2 μm cca-1.1, similar to 0.8 μm pgv-1, induced cell cycle arrest specifically at mitosis after 24 h. cca-1.1 induced cellular senescence and increased ros production following 24 h incubation. a notable distinction between the two compounds lies in their respective effects on cell cycle progression. pgv-1 induced cell arrest at the prometaphase by 80% (p=0.0001), whereas cca-1.1 was found to elicit around 20% of total cell arrest specifically at the metaphase (p=0.0035). immunoblot experiments provided evidence that 24h treatment of cca-1.1 tended to sustain the expression of p-cyclin b1, but pgv-1 led to an increase in the expression of p-cyclin b1 (p=0.0178) and p-plk1 (p=0.0051). conclusion: the findings from our study provide evidence for the molecular mechanism on mitotic kinases of cca-1.1 and pgv-1, resulting in the inhibition of the proliferation of leukemia cells during mitosis. furthermore, cca-1.1 induces mitotic catastrophe, leading to cellular death in k-562 cells.
کلیدواژه antimitotic agents ,cellular senescence ,chronic myeloid leukemia ,curcumin analogs ,m phase cell cycle arrest ,mitotic index
آدرس universitas gadjah mada, faculty of pharmacy, cancer chemoprevention research center, department of pharmaceutical chemistry, indonesia, universitas gadjah mada, cancer chemoprevention research center, faculty of pharmacy, indonesia. universitas padjadjaran, faculty of pharmacy, department of pharmaceutical analysis and medicinal chemistry, indonesia. nara institute of science and technology, graduate school of science and technology, laboratory of tumor cell biology, division of biological science, japan, universitas gadjah mada, cancer chemoprevention research center, faculty of pharmacy, department of pharmacology and clinical pharmacy, indonesia, universitas gadjah mada, faculty of pharmacy, cancer chemoprevention research center, department of pharmaceutical chemistry, indonesia, nara institute of science and technology, graduate school of science and technology, laboratory of tumor cell biology, division of biological science, japan, nara institute of science and technology, graduate school of science and technology, laboratory of tumor cell biology, division of biological science, japan, nara institute of science and technology, graduate school of science and technology, laboratory of tumor cell biology, division of biological science, japan, universitas gadjah mada, faculty of pharmacy, cancer chemoprevention research center, department of pharmaceutical chemistry, indonesia
پست الکترونیکی edy_meiyanto@ugm.ac.id
 
     
   
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