Khat induces G1-phase arrest and increased expression of stress-sensitive p53 and p16 proteins in normal human oral keratinocytes and fibroblasts

European Journal of Oral Sciences

Volumn 116, Issue 1, 2008, Pages 23-30

  Lukandu, Ochiba M ^a   Costea, Daniela E ^a   Dimba, Elizabeth A ^b   Neppelberg, Evelyn ^a   Bredholt, Therese ^a   Gjertsen, Bjørn T ^a   Vintermyr, Olav K ^a   Johannessen, Anne C ^a  

^a UNIVERSITY OF BERGEN   (Norway)

^b UNIVERSITY OF NAIROBI   (Kenya)

Author keywords

Cell cycle; Khat; Oral fibroblasts; Oral keratinocytes; Senescence

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1A; PLANT EXTRACT; PROTEIN P53;

ADULT; ANIMAL; ARTICLE; CATHA EDULIS; CATTLE; CELL CYCLE G1 PHASE; CELL DIFFERENTIATION; CELL PROLIFERATION; CYTOLOGY; DOSE RESPONSE; DRUG EFFECT; FEMALE; FIBROBLAST; HUMAN; KERATINOCYTE; MALE; MOUTH MUCOSA; TIME; TUMOR SUPPRESSOR GENE;

ADULT; ANIMALS; CATHA; CATTLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FIBROBLASTS; G1 PHASE; GENES, P16; HUMANS; KERATINOCYTES; MALE; MOUTH MUCOSA; PLANT EXTRACTS; TIME FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 38049007112     PISSN: 09098836     EISSN: 16000722     Source Type: Journal    
DOI: 10.1111/j.1600-0722.2007.00508.x     Document Type: Article

References (37)

1. Kalix P, Geisshusler S, Brenneisen R, Koelbing U, Fisch HU. Cathinone, a phenylpropylamine alkaolid from khat leaves that has amphetamine effects in humans. NIDA Res Monogr 1990 105 : 289 290.
2. Al-Motarreb A, Baker K, Broadley KJ. Khat: pharmacological and medical aspects and its social use in Yemen. Phytother Res 2002 16 : 403 413.
3. Odenwald M, Neuner F, Schauer M, Elbert T, Catani C, Lingenfelder B, Hinkel H, Hafner H, Rockstroh B. Khat use as risk factor for psychotic disorders: a cross-sectional and case-control study in Somalia. BMC Med 2005 3 : 5.
4. Raja'a Ya, Noman TA, Al Warafi AK, Al Mashraki NA, Al Yosofi AM. Khat chewing is a risk factor of duodenal ulcer. East Mediterr Health J 2001 7 : 568 570.
5. Al-Motarreb A, Briancon S, Al-Jaber N, Al-Adhi B, Al-Jailani F, Salek MS, Broadley Kj. Khat chewing is a risk factor for acute myocardial infarction: a case-control study. Br J Clin Pharmacol 2005 59 : 574 581.
6. Islam MW, Tariq M, Ageel AM, El-Feraly FS, Al-Meshal IA, Ashraf I. An evaluation of the male reproductive toxicity of cathinone. Toxicology 1990 60 : 223 234.
7. Hill CM, Gibson A. The oral and dental effects of q'at chewing. Oral Surg Oral Med Oral Pathol 1987 63 : 433 436.
8. Gorsky M, Epstein JB, Levi H, Yarom N. Oral white lesions associated with chewing khat. Tobac induced dis 2004 2 : 145 150.
9. Toennes SW, Harder S, Schramm M, Niess C, Kauert GF. Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. Br J Clin Pharmacol 2003 56 : 125 130.
10. Ali AA, Al-Sharabi AK, Aguirre JM, Nahas R. A study of 342 oral keratotic white lesions induced by qat chewing among 2500 Yemeni. J Oral Pathol Med 2004 33 : 368 372.
11. Dimba EA, Gjertsen BT, Bredholt T, Fossan KO, Costea DE, Francis GW, Johannessen AC, Vintermyr OK. Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells. Br J Cancer 2004 91 : 1726 1734.
12. Kassie F, Darroudi F, Kundi M, Schulte-Hermann R, Knasmuller S. Khat (Catha edulis) consumption causes genotoxic effects in humans. Int J Cancer 2001 92 : 329 332.
13. Nasr AH, Khatri ML. Head and neck squamous cell carcinoma in Hajjah, Yemen. Saudi Med J 2000 21 : 565 568.
14. Soufi HE, Kameswaran M, Malatani T. Khat and oral cancer. J Laryngol Otol 1991 105 : 643 645.
15. Tariq M, Parmar NS, Qureshi S, El-Feraly FS, Al-Meshal IA. Clastogenic evaluation of cathinone and amphetamine in somatic cells of mice. Mutat Res 1987 190 : 153 157.
16. De-Hondt HE, Fahmy AM, Abdelbaset SA. Chromosomal and biochemical studies on the effect of kat extract on laboratory rats. Environ Mutagen 1984 6 : 851 860.
17. Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007 8 : 275 283.
18. Stewart ZA, Pietenpol JA. p53 Signaling and cell cycle checkpoints. Chem Res Toxicol 2001 14 : 243 263.
19. Yook JI, Kim J. Expression of p21WAF1/CIP1 is unrelated to p53 tumour suppressor gene status in oral squamous cell carcinomas. Oral Oncol 1998 34 : 198 203.
20. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997 88 : 593 602.
21. Narita M, Lowe SW. Senescence comes of age. Nat Med 2005 11 : 920 922.
22. Lowe SW, Sherr CJ. Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev 2003 13 : 77 83.
23. Shintani S, Mihara M, Nakahara Y, Kiyota A, Ueyama Y, Matsumura T, Wong DT. Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity. Oral Oncol 2002 38 : 235 243.
24. Lee G, Park BS, Han SE, Oh JE, You YO, Baek JH, Kim GS, Min BM. Concurrence of replicative senescence and elevated expression of p16(INK4A) with subculture-induced but not calcium-induced differentiation in normal human oral keratinocytes. Arch Oral Biol 2000 45 : 809 818.
25. Weinberg WC, Denning MF. P21Waf1 control of epithelial cell cycle and cell fate. Crit Rev Oral Biol Med 2002 13 : 453 464.
26. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci USA 1996 93 : 13742 13747.
27. Costea DE, Dimba AO, Loro LL, Vintermyr OK, Johannessen AC. Proliferation and differentiation in organotypic serum free cultures of normal human oral mucosa. In : Varma AK, Kowalski LP, eds. 8th international conference on oral cancer; 2002; Rio de jane. Brazil : Rajkamal Electric press, 2002 108 113.
28. Vintermyr OK, Boe R, Brustugun OT, Maronde E, Aakvaag A, Doskeland SO. Cyclic adenosine monophosphate (cAMP) analogs 8-Cl- and 8-NH2-cAMP induce cell death independently of cAMP kinase-mediated inhibition of the G1/S transition in mammary carcinoma cells (MCF-7). Endocrinology 1995 136 : 2513 2520.
29. Carvalho F. The toxicological potential of khat. J Ethnopharmacol 2003 87 : 1 2.
30. Al-Meshal IA. Mitodepressive effect of (-)-cathinone, from Catha edulis (khat), on the meristematic region of Allium cepa root tips. Toxicon 1987 25 : 451 454.
31. Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature 2004 432 : 307 315.
32. Vousden KH. Activation of the p53 tumor suppressor protein. Biochim Biophys Acta 2002 1602 : 47 59.
33. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005 120 : 513 522.
34. Sharpless NE, Depinho RA. Cancer: crime and punishment. Nature 2005 436 : 636 637.
35. Ali AA, Al-Sharabi AK, Aguirre JM. Histopathological changes in oral mucosa due to takhzeen al-qat: a study of 70 biopsies. J Oral Pathol Med 2006 35 : 81 85.
36. Nordgarden H, Jensen JL, Storhaug K. Oligodontia is associated with extra-oral ectodermal symptoms and low whole salivary flow rates. Oral Dis 2001 7 : 226 232.
37. Vissink A, Kalk WW, Mansour K, Spijkervet FK, Bootsma H, Roodenburg JL, Kallenberg CG, Nieuw AV. Comparison of lacrimal and salivary gland involvement in Sjogren's syndrome. Arch Otolaryngol Head Neck Surg 2003 129 : 966 971.