COMPARATIVE EVALUATION OF MULTIDRUG RESISTANCE AND APOPTOSIS IN DIFFERENT VARIANTS OF HEPATOMA CELLS
DOI:
https://doi.org/10.71336/jabs.1069Keywords:
Apoptosis, Clone 2 cells, H56 cell lines, Hepatoma cells, P-glycoprotein, Multidrug ResistanceAbstract
Multidrug Resistance is a major obstacle in cancer chemotherapy. The current study was designed to evaluate the multidrug resistance and apoptotic properties of Hepatoma cells. Antiproliferative effect of five anti-cancer drugs: three of bacterial origin namely, puromycin, actinomycin D, doxorubicin and two plant derived drugs viz., colchicine and vinblastine were assessed on heat- resistant variants of dexamethasone–resistant and the dexamethasone- sensitive variants of hepatoma cell lines. These variants showed increased drug resistance to the different anticancer drugs used, i.e., they became moderately multidrug-resistant. The severely heat-treated H56 cells became moderately resistant only to certain drugs. All the experimental variants of Hepatoma cells overexpressed functional P-glycoprotein, a drug-resistant associated marker protein, which attributes to the resistance shown by these cells. The anticancer drugs were capable of inducing apoptosis in both H56 and clone 2 cells and it was found that H56 cells were more prone to undergo apoptosis as compared to clone 2 cells. Furthermore, preliminary immunocytochemical studies revealed that there was a significant difference in expression of p53, a tumor suppressor gene, in H56 and clone 2 cells where H56 cells showed very strong staining for p53 thereby justifying their proneness to apoptosis.
References
Baguley, B. C. (2010): Multidrug resistance in cancer. Multi-Drug Resistance in Cancer, 1–14. DOI: https://doi.org/10.1007/978-1-60761-416-6_1
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., Gottesman, M. M. (2006): Targeting multidrug resistance in cancer. Nature Reviews Drug Discovery 5(3), 219–234. DOI: https://doi.org/10.1038/nrd1984
Holohan, C., van Schaeybroeck, S., Longley, D. B., Johnston, P. G. (2013): Cancer drug resistance: an evolving paradigm. Nature Reviews Cancer 13(10), 714–726. DOI: https://doi.org/10.1038/nrc3599
Ozpolat, B. (2009): Resistance to differentiation therapy. In Drug resistance in cancer cells (pp. 233–255). Springer. DOI: https://doi.org/10.1007/978-0-387-89445-4_10
Fan, D., Kim, S.-J., Langley, R. L., Fidler, I. J. (2009): Metastasis and drug resistance. In Drug Resistance in Cancer Cells (pp. 21–52). Springer. DOI: https://doi.org/10.1007/978-0-387-89445-4_2
Ye, Q., Liu, K., Shen, Q., Li, Q., Hao, J., Han, F., Jiang, R.-W. (2019): Reversal of multidrug resistance in cancer by multi-functional flavonoids. Frontiers in Oncology 9, 487. DOI: https://doi.org/10.3389/fonc.2019.00487
Li, W., Zhang, H., Assaraf, Y. G., Zhao, K., Xu, X., Xie, J., Yang, D. H., Chen, Z. S. (2016): Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies. In Drug Resistance Updates (Vol. 27, pp. 14–29). Churchill Livingstone. https://doi.org/10.1016/j.drup.2016.05.001 DOI: https://doi.org/10.1016/j.drup.2016.05.001
Xue, M., Cheng, J., Zhao, J., Zhang, S., Jian, J., Qiao, Y., Liu, B. (2019): Outcomes of 219 chronic myeloid leukaemia patients with additional chromosomal abnormalities and/or tyrosine kinase domain mutations. International Journal of Laboratory Hematology 41(1), 94–101. DOI: https://doi.org/10.1111/ijlh.12928
Tiribelli, M., Latagliata, R., Luciano, L., Castagnetti, F., Gozzini, A., Cambrin, G. R., Annunziata, M., Stagno, F., Pregno, P., Albano, F. (2013): Impact of BCR-ABL mutations on response to dasatinib after imatinib failure in elderly patients with chronic-phase chronic myeloid leukemia. Annals of Hematology 92(2), 179–183. DOI: https://doi.org/10.1007/s00277-012-1591-2
Taylor, S., Spugnini, E. P., Assaraf, Y. G., Azzarito, T., Rauch, C., Fais, S. (2015): Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resistance Updates 23, 69–78. DOI: https://doi.org/10.1016/j.drup.2015.08.004
Yeldag, G., Rice, A., del Río Hernández, A. (2018): Chemoresistance and the self-maintaining tumor microenvironment. Cancers 10(12), 471. DOI: https://doi.org/10.3390/cancers10120471
Prieto-Vila, M., Takahashi, R., Usuba, W., Kohama, I., Ochiya, T. (2017): Drug resistance driven by cancer stem cells and their niche. International Journal of Molecular Sciences 18(12), 2574. DOI: https://doi.org/10.3390/ijms18122574
Koren, E., Fuchs, Y. (2016): The bad seed: Cancer stem cells in tumor development and resistance. Drug Resistance Updates 28, 1–12. DOI: https://doi.org/10.1016/j.drup.2016.06.006
Endicott, J. A., Ling, V. (1989): The biochemistry of P-glycoprotein-mediated multidrug resistance. Annual Review of Biochemistry 58(1), 137–171. DOI: https://doi.org/10.1146/annurev.biochem.58.1.137
Gottesman, M. M. (1993): How cancer cells evade chemotherapy: sixteenth Richard and Hinda Rosenthal Foundation award lecture. Cancer Research 53(4), 747–754.
Lage, H. (2008): An overview of cancer multidrug resistance: a still unsolved problem. Cellular and Molecular Life Sciences 65(20), 3145–3167. DOI: https://doi.org/10.1007/s00018-008-8111-5
Waghray, D., Zhang, Q. (2017): Inhibit or evade multidrug resistance P-glycoprotein in cancer treatment: Miniperspective. Journal of Medicinal Chemistry 61(12), 5108–5121. DOI: https://doi.org/10.1021/acs.jmedchem.7b01457
Bukowski, K., Kciuk, M., Kontek, R. (2020): Mechanisms of multidrug resistance in cancer chemotherapy. International Journal of Molecular Sciences 21(9), 3233. DOI: https://doi.org/10.3390/ijms21093233
Juliano, R. L., Ling, V. (1976): A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochimica et Biophysica Acta (BBA)-Biomembranes 455(1), 152–162. DOI: https://doi.org/10.1016/0005-2736(76)90160-7
Hamada, H., Tsuruo, T. (1988): Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Research 48(17), 4926–4932.
Naito, M., Hamada, H., Tsuruo, T. d. (1988): ATP/Mg2+-dependent binding of vincristine to the plasma membrane of multidrug-resistant K562 cells. Journal of Biological Chemistry 263(24), 11887–11891. DOI: https://doi.org/10.1016/S0021-9258(18)37869-4
Horio, M., Gottesman, M. M., Pastan, I. (1988): ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proceedings of the National Academy of Sciences 85(10), 3580–3584. DOI: https://doi.org/10.1073/pnas.85.10.3580
Gottesman, M. M., Ling, V. (2006): The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Letters 580(4), 998–1009. DOI: https://doi.org/10.1016/j.febslet.2005.12.060
Hegyi, G., Szigeti, G. P., Szasz, O., Szasz, A. (2013): Hyperthermia versus Oncothermia: cellular effects in cancer therapy. Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 274687, 4 pages. DOI: https://doi.org/10.1155/2013/274687
Behrouzkia, Z., Joveini, Z., Keshavarzi, B., Eyvazzadeh, N., Aghdam, R. Z. (2016): Hyperthermia: how can it be used? Oman Medical Journal 31(2), 89. DOI: https://doi.org/10.5001/omj.2016.19
Lutgens, L., van der Zee, J., Pijls‐Johannesma, M., de Haas‐Kock, D. F. M., Buijsen, J., van Mastrigt, G. A. P. G., Lammering, G., de Ruysscher, D. K. M., Lambin, P. (2010): Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma. Cochrane Database of Systematic Reviews 3. DOI: https://doi.org/10.1002/14651858.CD006377.pub2
Bettaieb, A., Wrzal, P. K., Averill-Bates, D. A. (2013): Hyperthermia: Cancer treatment and beyond. Cancer Treatment-Conventional and Innovative Approaches 257–283. DOI: https://doi.org/10.5772/55795
Engelhardt, R. (1987): Hyperthermia and drugs. Hyperthermia and the Therapy of Malignant Tumors 136–203. DOI: https://doi.org/10.1007/978-3-642-82955-0_5
Hahn, G. M. (1990): Thermotolerance, thermoresistance, and thermosensitization. Stress Proteins in Biology and Medicine 79–100.
Urano, M., Douple, E. (1994): Hyperthermia and Oncology Vol. 4, Chemopotentiation by Hyperthermia. VSP Utrecht: The Netherlands.
Dahl, O. (1995): Interaction of heat and drugs in vitro and in vivo. In Thermoradiotherapy and thermochemotherapy (pp. 103–121). Springer. DOI: https://doi.org/10.1007/978-3-642-57858-8_5
Gerner, E. W., Schneider, M. J. (1975): Induced thermal resistance in HeLa cells. Nature 256(5517), 500–502. DOI: https://doi.org/10.1038/256500a0
Subjeck, J. R., Sciandra, J. J., & Johnson, R. J. (1982): Heat shock proteins and thermotolerance; a comparison of induction kinetics. The British Journal of Radiology 55(656), 579–584. DOI: https://doi.org/10.1259/0007-1285-55-656-579
Samali, A., Cotter, T. G. (1996): Heat shock proteins increase resistance to apoptosis. Experimental Cell Research 223(1), 163–170. DOI: https://doi.org/10.1006/excr.1996.0070
Landry, J., Chrétien, P., Bernier, D., Nicole, L. M., Marceau, N., Tanguay, R. M. (1982): Thermotolerance and heat shock proteins induced by hyperthermia in rat liver cells. International Journal of Radiation Oncology* Biology* Physics 8(1), 59–62. DOI: https://doi.org/10.1016/0360-3016(82)90385-6
Martindale, J. L., Holbrook, N. J. (2002): Cellular response to oxidative stress: signaling for suicide and survival. Journal of Cellular Physiology 192(1), 1–15. DOI: https://doi.org/10.1002/jcp.10119
Rhee, J. G., Schuman, V. L., Song, C. W., Levitt, S. H. (1987): Difference in the thermotolerance of mouse mammary carcinoma cells in vivo and in vitro. Cancer Research 47(10), 2571–2575.
Müller, M., Strand, S., Hug, H., Heinemann, E.-M., Walczak, H., Hofmann, W. J., Stremmel, W., Krammer, P. H., Galle, P. R. (1997): Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. The Journal of Clinical Investigation 99(3), 403–413. DOI: https://doi.org/10.1172/JCI119174
Sen, S., D’Incalci, M. (1992): Apoptosis biochemical events and relevance to cancer chemotherapy. FEBS Letters 307(1), 122–127. DOI: https://doi.org/10.1016/0014-5793(92)80914-3
Golstein, P. (1997): Controlling cell death. Science 275(5303), 1081–1082. DOI: https://doi.org/10.1126/science.275.5303.1081
Fisher, D. E. (1994): Apoptosis in cancer therapy: crossing the threshold. Cell 78(4), 539–542. DOI: https://doi.org/10.1016/0092-8674(94)90518-5
Richter, K., Haslbeck, M., Buchner, J. (2010): The heat shock response: life on the verge of death. Molecular Cell 40(2), 253–266. DOI: https://doi.org/10.1016/j.molcel.2010.10.006
Calderwood, S. K., Mambula, S. S., Gray Jr, P. J. (2007): Extracellular heat shock proteins in cell signaling and immunity. Annals of the New York Academy of Sciences 1113(1), 28–39. DOI: https://doi.org/10.1196/annals.1391.019
Landry, J., Bernier, D., Chrétien, P., Nicole, L. M., Tanguay, R. M., Marceau, N. (1982): Synthesis and degradation of heat shock proteins during development and decay of thermotolerance. Cancer Research 42(6), 2457–2461.
Hayashi, M., Koike, K., Kuwano, M., Kishiye, T., Komiyama, K. (2001): Reversal of P‐glycoprotein associated multidrug resistance by new isoprenoid derivatives. Anti-Cancer Drug Design 16(4), 255–260.
Kregel, K. C. (2002): Invited review: heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. Journal of Applied Physiology 92(5), 2177–2186. DOI: https://doi.org/10.1152/japplphysiol.01267.2001
Bettaieb, A., Averill‐Bates, D. A. (2005): Thermotolerance induced at a mild temperature of 40° C protects cells against heat shock‐induced apoptosis. Journal of Cellular Physiology 205(1), 47–57. DOI: https://doi.org/10.1002/jcp.20386
Venetianer, A., Pirity, M., Hever-Szabo, A. (1994): The function of heat-shock proteins in stress tolerance. Cell Biology International 18(6), 605–616. DOI: https://doi.org/10.1006/cbir.1994.1087
Pirity, M., Hevér-Szabó, A., Venetianer, A. (1996): Overexpression of P-glycoprotein in heat-and/or drug-resistant hepatoma variants. Cytotechnology 19(3), 207–214. DOI: https://doi.org/10.1007/BF00744214
Reuber, M. D. (1961): A transplantable bile-secreting hepatocellular carcinoma in the rat. Journal of the National Cancer Institute 26(4), 891–899.
Pitot, H. C. (1964): Hepatoma in tissued culture compared with adapting liver in vitro. Natl. Cancer Inst. Monogr. 13, 229–242.
Deschatrette, J., Weiss, M. C. (1975): Characterization of differentiated and dedifferentiated clones from a rat hepatoma. Biochimie 56(11–12), 1603–1611. DOI: https://doi.org/10.1016/S0300-9084(75)80286-0
Venetianer, A., Pintér, Z., Gal, A. (1980): Examination of glucocorticoid sensitivity and receptor content of hepatoma cell lines. Cytogenetic and Genome Research 28(4), 280–283. DOI: https://doi.org/10.1159/000131541
Fardel, O., Lecureur, V., Guillouzo, A. (1993): Regulation by dexamethasone of P‐glycoprotein expression in cultured rat hepatocytes. FEBS Letters 327(2), 189–193. DOI: https://doi.org/10.1016/0014-5793(93)80167-S
Bonfoco, E., Ceccatelli, S., Manzo, L., Nicotera, P. (1995): Colchicine induces apoptosis in cerebellar granule cells. Experimental Cell Research 218(1), 189–200. DOI: https://doi.org/10.1006/excr.1995.1147
Akimoto, H., Bruno, N. A., Slate, D. L., Billingham, M. E., Torti, S. V, Torti, F. M. (1993): Effect of verapamil on doxorubicin cardiotoxicity: altered muscle gene expression in cultured neonatal rat cardiomyocytes. Cancer Research 53(19), 4658–4664.
Germann, U. A., Ford, P. J., Shlyakhter, D., Mason, V. S., Harding, M. W. (1997): Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. Anti-Cancer Drugs 8(2), 141–155. DOI: https://doi.org/10.1097/00001813-199702000-00005
Qadir, M., O’Loughlin, K. L., Fricke, S. M., Williamson, N. A., Greco, W. R., Minderman, H., Baer, M. R. (2005): Cyclosporin A is a broad-spectrum multidrug resistance modulator. Clinical Cancer Research 11(6), 2320–2326. DOI: https://doi.org/10.1158/1078-0432.CCR-04-1725
le Bot, M. A., Kernaleguen, D., Simon, I., Berlion, M., Riche, C. (1996): Effect of S9788, cyclosporin A and verapamil on intracellular accumulation of doxorubicin, daunorubicin and daunorubicinol in primary rat hepatocyte culture. Annales de Biologie Clinique 54(1), 21–24.
Sebille, S., Morjani, H., Poullain, M. G., Manfait, M. (1994): Effect of S9788, cyclosporin A and verapamil on intracellular distribution of THP-doxorubicin in multidrug-resistant K562 tumor cells, as studied by laser confocal microspectrofluorometry. Anticancer Research, 14(6A) 2389–2393.
van der Bliek, A. M., van der Velde-Koerts, T., Ling, V., Borst, P. (1986): Overexpression and amplification of five genes in a multidrug-resistant Chinese hamster ovary cell line. Molecular and Cellular Biology 6(5), 1671–1678. DOI: https://doi.org/10.1128/mcb.6.5.1671-1678.1986
Fojo, A. T., Ueda, K., Slamon, D. J., Poplack, D. G., Gottesman, M. M., Pastan, I. (1987): Expression of a multidrug-resistance gene in human tumors and tissues. Proceedings of the National Academy of Sciences 84(1), 265–269. DOI: https://doi.org/10.1073/pnas.84.1.265
Scheper, R. J., Bulte, J. W. M., Brakkee, J. G. P., Quak, J. J., van der Schoot, E., Balm, A. J. M., Melier, C., Broxteman, H. J., Kuiper, C. M., Lankelma, J. (1988): Monoclonal antibody JSB‐1 detects a highly conserved epitope on the P‐glycoprotein associated with multi‐drug‐resistance. International Journal of Cancer 42(3), 389–394. DOI: https://doi.org/10.1002/ijc.2910420314
Juranka, P. F., Zastawny, R. L., Ling, V. (1989): P‐glycoprotein: multidrug‐resistance and a superfamily of membrane‐associated transport proteins. The FASEB Journal 3(14), 2583–2592. DOI: https://doi.org/10.1096/fasebj.3.14.2574119
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Journal of Applied Biological Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
