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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: CML,imatinib,D. pentandra,BCR/ABL,K562
- چکیده:
- چکیده انگلیسی:
Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.- انتشار مقاله: 02-06-1395
- نویسندگان: Afiqah Zamani,Siti Asmaa Mat Jusoh,Hamid Ali Nagi Al-Jamal,Mohd Dasuki Sul’ain,Muhammad Farid Johan
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Pyrrosia piloselloides,anti-proliferative,Hela cell lines
- چکیده:
- چکیده انگلیسی: Background: Cervical cancer is one of the most commonly diagnosed neoplasms and a leading cause of cancer
death among females worldwide. Limitations with conventional medical treatments have driven researchers to
search for alternative approaches using natural products. This study aimed to detemine potential anti-proliferative
effects of methanol and water extracts of Pyrrosia piloselloides (P. piloselloides) on the HeLa cell line. Methods:
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine IC50
concentrations and apoptosis analysis was by flow cytometry. To identify chemical compounds in the extracts, gas
chromatography-mass spectrometry (GC-MS) was employed. Results: P. piloselloides methanol extracts (PPME) showed
antiproliferative effects on HeL awith an IC50 of 16.25μg/mL while the P. piloselloides water extract (PPWE) was without
influence. Neither extract showed any significant effects on apoptosis. GC-MS analysis, revealed 5-hydroxymethylfurfural
(23.1%), allopurinol (8.66%) and 3, 5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (7.41%) as major components in
the PPME, while sulfolan-3-ol (10.1%), linoleic acid (9.06%) and β-sitosterol acetate (7.98%) predominated in the
PPWE case. Conclusion: This first study of P. piloselloides showed PPME to exert potent anti-proliferative effect on
HeLa cell lines. Further research now needs to be performed to establish the mechanisms of inhibition.- انتشار مقاله: 26-04-1397
- نویسندگان: Mohd Dasuki Sul ‘ain,Fashihah Zakaria,Muhammad Farid Johan
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: CML,imatinib,PRG2,5-Azacytidine,STAT3
- چکیده:
- چکیده انگلیسی: Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in development and
progression of cancers. Re-expression of TSG is inversely proportionate with STAT3 signaling pathways.
Demethylation of DNA by 5-Azacytidine (5-Aza) results in re-expression of silenced TSG. Forced expression of
PRG2 by 5-Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor that potently inhibits BCR/
ABL tyrosine kinase resulting in hematological remission in CML patients. However, majority of CML patients treated
with imatinib would develop resistance under prolonged therapy. Methods: CML cells resistant to imatinib were
treated with 5-Aza and cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively.
Gene expression analysis was detected by real time-PCR, STATs activity examined using Western blot and methylation
status of PRG2 was determined by pyrosequencing analysis. Result: Expression of PRG2 was significantly higher in
K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreased
in K562-R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562-R+5-Aza cells which showed
higher sensitivity to imatinib. Conclusion: PRG2 gene is a TSG and its overexpression might induce sensitivity to
imatinib. However, further studies are required to evaluate the negative regulations of PRG2 on STAT3 signaling.- انتشار مقاله: 17-08-1396
- نویسندگان: Hamid Ali Nagi Al-Jamal,Muhammad Farid Johan,Siti Asmaa Mat Jusoh,Imilia Ismail,Wan Rohani Wan Taib
- مشاهده