2000, Number 4
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Rev Inst Nal Enf Resp Mex 2000; 13 (4)
Effects of cumarine and 7-hydroxicumarine on the cell cycle of pulmonary adenocarcinoma cell lines.
Sullivan López-González J, Prado GH, Aguilar CD, Molina GJA, Mandoki JJ, Medina MF
Language: Spanish
References: 26
Page: 192-197
PDF size: 55.69 Kb.
ABSTRACT
Introduction: Coumarins are compounds widely distributed in nature. In humans, the main metabolite of coumarin is 7-hydroxicoumarin. These compounds show antitumoral activity in vivo and in vitro. We previously reported that coumarin and 7-hydroxicoumarin have cytostatic activity in adenocarcinoma cell lines; however, no reports are available concerning the cell cycle phase in which these compounds may act.
Objective: To determine the effect of coumarin and 7-hydroxicoumarin on the cell cycle transition in lung adenocarcinoma cell lines.
Material and methods. Three adenocarcinoma cell lines (SK-LU-1, 1.3.15, 3A5A) and healthy donor mononuclear cells stimulated with phytohemagglutinin were incubated for 24h and 40h respectively with 100 mg/mL of coumarin or 7-hydroxicoumarin. Cell cycle disturbances were evaluated by flow cytometry using DNA content analysis.
Results: After treatment, the cell lines showed statistically significant accumulation of the G0/GI cell cycle phase, accompanied by a proportional depletion of the S-phase. Nevertheless, no significant changes were observed in mononuclear cells after treatment.
Conclusions: Results show that coumarin and 7-hydroxicoumarin arrest tumoral cells at the G0/GI phase. Understanding the cell cycle disturbances induced by these compounds will help in the design of treatment schedules by combination with other drugs that arrest the cell cycle at other phases. Furthermore, this methodology can be used to test tumor cell susceptibility against chemotherapeutic agents.
REFERENCES
Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudaira P, Darnell J. Molecular cell biology. 3rd ed. New York: Scientific American Books, 1995: 1201-1245.
Rowinski E, Ettinger D. Drug development and new drugs for lung cancer. In: Pass H, Mitchell JB, Johnson DH, editors. Lung cancer. Philadelphia: Lippincott-Raven, 1996: 793-810.
Lazcano P, Tovar GV, Meneses GF, Rascón PRA, Hernández AM. Trends of lung cancer mortality in Mexico. Arch Med Res 1997; 28: 565-570.
Natale RB. Experience with new chemotherapeutic agents in non-small cell lung cancer. Chest 1998; 113: 32S-39S.
O’Kennedy R, Thornes RD. Coumarins, biology, applications and mode of action. England: John Wiley and Sons, 1997; 23-27, 67-75.
Wattenberg LW, Lam LK, Fladmoe AV. Inhibition of chemical carcinogen-induced neoplasia by coumarins and alpha-angelicalactone. Cancer Res 1979; 39: 1651-1654.
Cai Y, Kleiner H, Johnson D, Dubowski A, Bostic S, Ivie W et al. Effect of naturally occurring coumarins on the formation of epidermal DNA adducts and skin tumors induced by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in SENCAR mice. Carcinogenesis 1997; 18: 1521-1527.
Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ, Forcier RJ, et al. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans administration study No 75. JAMA 1981; 245: 831-835.
Thornes RD, Daly L, Lynch G, Breslin B, Browne H, Browne HY, et al. Treatment with coumarin to prevent or delay recurrence of malignant melanoma. J Cancer Res Clin Oncol 1994; 120(Suppl): 32S-34S.
Marshall ME, Mendelsohn L, Butler K, Riley K, Cantrell J, Wiseman C, et al. Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: A pilot study. J Clin Oncol 1987; 5: 862-866.
Mohler JL, Williams BT, Thompson IM, Marshall ME. Coumarin (1,2-benzopyrone) for the treatment of prostatic carcinoma. J Cancer Res Clin Oncol 1994; 120 (Suppl): 35S-38S.
Von Angerer E, Kager M, Maucher A. Antitumor activity of coumarin in prostate and mammary cancer models. J Cancer Res Clin Oncol 1994; 120(Suppl): 14S-16S.
Rosskopf F, Kraus J, Franz G. Immunological and antitumor effects of coumarin and some derivatives. Pharmazie 1992; 47: 139-142.
Grigg GW. Genetics effects of coumarins. Mutation Res 1978; 47: 161-181.
Seliger B, Petterson H. 7-Hidroxycoumarin inhibits oncogene-induced transformation of murine fibroblast. J Cancer Res Clin Oncol 1994; 120(Suppl): 23S-27S.
Marshall ME, Kervin K, Benefield C, Umerani A, Albainy-Jenei S, Zhao Q, et al. Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro. J Cancer Res Clin Oncol 1994; 120(Suppl): 3S-10S.
Myers RB, Parker M, Grizzle WE. The effects of coumarin and suramin on the growth of malignant renal and prostatic cell lines. J Cancer Res Clin Oncol 1994; 120(Suppl): 11S-13S.
García HV. Efecto citostático de la cumarina y la 7-hidroxicumarina en distintas líneas celulares de cáncer de pulmón. [Tesis] México: UNAM, Facultad de Química, 1999.
López-González JS, García HV, Aguilar CD, Medina MF, Mendieta CI, Rosales R RS, et al. Efecto citostático de la cumarina y la 7-hidroxicumarina en tres líneas celulares de adenocarcinoma pulmonar humano. Rev Inst Nal Enf Resp Mex 1998; 11: 261-267.
Tolis C, Peters GJ, Ferreira CG, Pinedo HM, Giaccone G. Cell cycle disturbances and apoptosis induced by topotecan and gemcitabine on human lung cancer cell lines. Eur J Cancer 1999; 35: 796-807.
Mastbergen SC, Duivenvoorden I, Versteegh RT, Geldof AA. Cell cycle arrest and clonogenic tumor cell kill by divergent chemotherapeutic drugs. Anticancer Res 2000; 20: 1833-1838.
Higgins PJ. Cell cycle phase-specific perturbation of hepatic tumor cell growth kinetics during short-term in vitro exposure to ethanol. Alcohol Clin Exp Res 1987; 11: 550-555.
Cook RT, Keiner J, Yen A, Fishbaugh J. Ethanol induced growth adaptation in vitro. Cell cycle delay in late G1. Alcohol Alcohol 1990; 25: 33-43.
Guo W, Baluda MA, Park NH. Ethanol upregulates the expression of p2 WAF1/CIP1 and prolongs G1 transition via a p53-independent pathway in human epithelial cells. Oncogene 1997; 15: 1143-1149.
Kubbies M, Schindler D, Hoenh H, Rabinovith PS. BrdU-Hoechts flow cytometry reveals regulation of human lymphocyte growth by donor-age-related growth fraction and transition rate. J Cell Physiol 1985; 125: 229-234.
Martin KJ, Winslow ER, Kaddurah-Daouk R. Cell cycles studies of cyclocreatine, a new anticancer agent. Cancer Res 1994; 54: 5160-5165.