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논문 기본 정보

자료유형
학술저널
저자정보
Suman Jyoti Deka (Malaria Research Group) Narsimha Mamdi (Indian Institute of Technology Guwahati) Debasis Manna (Indian Institute of Technology Guwahati) Vishal Trivedi (Malaria Research Group)
저널정보
한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.19 No.4
발행연도
2016.1
수록면
358 - 371 (14page)

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Purpose: The protein kinase C (PKC) family of serine-threonine kinases plays an important role in cancer cell progression. Thus, molecules that target PKC have potential as anticancer agents. The current study aims to understand the treatment of breast cancer cells with alkyl cinnamates. We have also explored the mechanistic details of their anticancer action and the underlying molecular signaling. Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure the viability of MDAMB-231 breast cancer cells to assess the anticancer activity of these compounds. In addition, flow cytometry was performed to study the effect of alkyl cinnamates on the cell cycle and apoptosis. Immunoblotting and immunofluorescence techniques were performed to study PKC translocation, cytochrome c release, and modulation of the mitochondrial membrane potential in breast cancer cells targeted with alkyl cinnamates. Results: The PKC agonist DM-2-8 translocated 16.6%±1.7% PKCα from cytosol to the plasma membrane and showed excellent anticancer activity with an half maximal inhibitory concentration (IC50) of 4.13±0.27 μg/mL against cancer cells. The treated cells had an abnormal morphology and exhibited cell cycle defects with G2/M arrest and reduced S phase. Cancer cells treated with DM-2-3, DM-2-4, or DM-2-8 underwent apoptosis as the major pathway of cell death, further confirmed by genomic DNA fragmentation. Furthermore, the mitochondrial membrane potential was perturbed, indicating involvement of the mitochondrial pathway of apoptosis. Immunolocalization studies revealed cytochrome c release from mitochondria to cytosol. Cancer cells treated with DM-2-8 and curcumin showed activation of caspase-9 and caspase-3 as downstream molecular components of the apoptotic pathway. Alkyl cinnamates also caused oxidative stress, which regulates the apoptotic machinery (DNA fragmentation), cell death, and morphological abnormalities in cancer cells. Conclusion: Alkyl cinnamates specifically target cancer cells through induction of PKC translocation and the mitochondrial pathway of apoptosis, and could be promising anticancer drugs.

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참고문헌 (30)

참고문헌 신청
Hanahan D / 2000 / The hallmarks of cancer / Cell 100:57~70 google schola Koivunen J / 2006 / Protein kinase C (PKC) family in cancer progression / Cancer Lett 235:1~10 google schola Griner EM / 2007 / Protein kinase C and other diacylglycerol effectors in cancer / Nat Rev Cancer 7:281~294 google schola O’Brian C / 1989 / Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue / Cancer Res 49:3215~3217 google schola Powell CT / 1996 / Persistent membrane translocation of protein kinase C alpha during 12-0-tetradecanoylphorbol-13-acetate-induced apoptosis of LNCaP human prostate cancer cells / Cell Growth Differ 7:419~428 google schola

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