Preventive Nutrition and Food Science

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Apoptosis of MCF7 Cells Treated with PKC Inhibitors and Daunorubicin

  • Park, Won-Chul (Dept. of Biology, College of Natural Sciences, Pusan National University) ;
  • Son, Joo-Young (Dept. of Biology, College of Natural Sciences, Pusan National University) ;
  • Chung, Sook-Hyun (Dept. of Food Engineering, Dongseo University) ;
  • An, Woon-Gun (Dept. of Biology, College of Natural Sciences, Kyungpook National University)
  • Published : 2002.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

The present study was performed to observe the role of protein kinase C (PKC) inhibitors (H-7, staurosporine) and daunorubicin in the cell death process of MCF7 cells; and examined whether or not the type of induced cell death was apoptosis. The usefulness of the combined therapy of PKC inhibitors and daunorubicin to improve the adverse effect of daunorubicin was also investigated. Cell death was induced by treatment with PKC inhibitors or daunorubicin. Characteristic morphologic features of cell shrinkage, chromatic condensation, and cytoplasmic vacuolization were observed. These treatments also stimulated the cleavage of poly-(ADP-ribose) polymerase (PARP), an early event in apoptosis. With slight differences in the percentage of apoptosis-induced cells, staurosporine, H-7 and daunorubicin effectively induced apoptosis in MCF7 cells. Furthermore, combined treatment of PKC inhibitors and daunorubicin significantly drove the cells into an apoptotic state. Hence, our results revealed the possible therapeutic value of combined therapy for the prevention of drug resistance and adverse side effects.

Keywords

References

  1. Ronca F, Chan SL, Yu VC. 1997. 1-(5-isoquinolinesulfonyl)-2-methylpiperazine induces apoptosis in human neuroblastoma cells, SH-SY5Y, through a p53-dependent pathway. J Biol Chem 272: 4252-4260 https://doi.org/10.1074/jbc.272.7.4252
  2. Shimizu T, Cao CX, Shao RG, Pommier Y. 1998. Lamin B phosphorylation by protein kinase C $\alpha$ and proteolysis during apoptosis in human leukemia HL60 cells. J Biol Chem 273: 8669-8674 https://doi.org/10.1074/jbc.273.15.8669
  3. Gooch JL, Yee D. 1999. Strain-specific differences information of apoptotic DNA Ladders in MCF-7 breast cancer cells. Cancer Lett 144: 31-35 https://doi.org/10.1016/S0304-3835(99)00208-6
  4. Janicke RU, Sprengart ML, Wati MR, Porter AG. 1998. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273: 9357-9360
  5. Lopez E, Ferrer I. 2000. Staurosporine- and H-7-induced cell death in SH-SY5Y neuroblastoma cells is associated with caspase-2 and caspase-3 activation, but not with activation of the FAS/FAS-L-caspase-8 signaling pathway. Mol Brain Res 85: 61-66 https://doi.org/10.1016/S0169-328X(00)00235-7
  6. Thompson CB. 1995. Apoptosis in the pathogenesis and treatment of disease. Science 267: 456-459 https://doi.org/10.1126/science.267.5197.456
  7. Harkin ST, Cohen GM, Gescher A. 1998. Modulation of apoptosis in rat thymocytes by analogs of staurosporine- lack of direct association with inhibition of protein kinase C. Mol Pharmacol 54: 663-670
  8. Ferraris C, Cooklis M, Polakowska RR, Haake AR. 1997. Induction of apoptosis through the PKC pathway in cultured dermal papilla fibroblast Exp Cell Res 234: 37-46 https://doi.org/10.1006/excr.1997.3601
  9. Bettaieb A, Plo I, Mansat DMV, Quillet MA, Levade T, Laurent G, Jaffrezou JP. 1999. Daunorubicin andmitoxantrone triggered phosphatidylcholine hydrolysis:implication in drug-induced ceramide generation and apoptosis. Mol Pharmacol 55: 118-125
  10. Garzotto M, Whitejones M, Jiang YW, Ehleiter D, Liaom WC, Haimovitzfriedman A, Fuks Z, Kolesnick R. 1998. 12-O-tetradecanoylphorbol-13-acetate-induced apoptosis in LNCap cells is mediated through ceramide synthase. Cancer Res 58: 2260-2264
  11. Mansat V, Laurent G, Levade T, Bettaieb A, Zaffrezou JP. 1997. The protein kinase C activators phorbol esters and phosphatidylserine inhibit neural sphingomyelinase activation, ceramide generation, and apoptosis triggered by daunorubicin. Cancer Res 57: 5300-5304
  12. Otzuka K, Yoshimizu, I. 1998. Visual biochemistry and molecular biology for life science. p 96-99
  13. Witty JP, Bridgham JY, Johnson AL. 1996. Induction of apoptosis is through the PKC pathway in cultured dermalpapillafibroblast. Endocrinol 137: 5269-5277 https://doi.org/10.1210/en.137.12.5269
  14. de Silva CP, de Oliveira CR, de Conceicao M, de Lima P. 1996. Apoptosis as a mechnism of cell death induced by different chemotherapeutic drugs in human T-lymphocytes. Biochem Pharmacol 51: 1331-1340 https://doi.org/10.1016/0006-2952(96)00041-X