Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment

Book chapter


Owen, H., Appiah, S., Hasan, N., Ghali, L., Elayat, G. and Bell, C. 2017. Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment. in: Zeng, B. and Zhao, K. (ed.) Neurobiology of Chinese Herb Medicine Elsevier.
Chapter titlePhytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment
AuthorsOwen, H., Appiah, S., Hasan, N., Ghali, L., Elayat, G. and Bell, C.
Abstract

Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as “sanctuaries” where \{LSCs\} acquire drug resistance. This review explores the role of the bone marrow environment in the maintenance of \{LSCs\} and its contribution to chemoresistance and considers current research on the potential use of phytochemicals to overcome chemoresistance through the modulation of signaling pathways involved in the survival and death of leukemic clonal cells and/or leukemic stem cells. Phytochemicals from traditional Chinese medicine, namely baicalein, chrysin, wogonin (constituents of Scutellaria baicalensis; huáng qín; 黄芩), curcumin (a constituent of Curcuma longa, jiāng huáng, 姜黄), and resveratrol (a constituent of Polygonum cuspidatum; hŭ zhàng, 虎杖) have been shown to induce apoptosis in leukemic cell lines, with curcumin and resveratrol also causing cell death via the induction of autophagy (a nonapoptotic pathway). In order to be effective in eliminating LSCs, it is important to target signaling pathways (such as Wnt/β-catenin, Notch, and Hedgehog). Resveratrol has been reported to induce apoptosis in leukemic cells through the inhibition of the Notch and Sonic hedgehog signaling pathways, therefore showing potential to affect LSCs. While these findings are of interest, there is a lack of reported research on the modulatory effect of phytochemicals on the autophagic cell death pathway in leukemia, and on the signaling pathways involved in the maintenance of LSCs, highlighting the need for further work in these areas.

LanguageEnglish
Book titleNeurobiology of Chinese Herb Medicine
EditorsZeng, B. and Zhao, K.
PublisherElsevier
Academic Press
SeriesInternational Review of Neurobiology
ISBN
Hardcover9780128117798
ISSN0074-7742
Electronic2162-5514
Publication dates
Online12 Apr 2017
Print17 Aug 2017
Publication process dates
Deposited10 May 2017
Accepted12 Apr 2017
Output statusPublished
Digital Object Identifier (DOI)https://doi.org/10.1016/bs.irn.2017.02.012
Web of Science identifierWOS:000414408000012
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Wen, S., Li, D., Ghali, L. and Iles, R. 2010. Ectopic HCG beta may induce epithelialmensenchymal transition on human kera tinocytes in vitro and this could promote tumour progression and invasion. Tumour Biology. 31 (S44).
GLI1 confers profound phenotypic changes upon LNCaP prostate cancer cells that include the acquisition of a hormone independent state
Nadenla, S., Hazan, A., Ward, M., Harper, L., Moutasim, K., Bianchi, L., Naase, M., Ghali, L., Thomas, G., Prowse, D., Philpott, M. and Neill, G. 2011. GLI1 confers profound phenotypic changes upon LNCaP prostate cancer cells that include the acquisition of a hormone independent state. PLoS ONE. 6 (5), pp. 1-13. https://doi.org/10.1371/journal.pone.0020271
Evaluation of herbs as potential alternatives for bear bile and rhino horn used in traditional Chinese medicines: chemical and biological analysis.
Appiah, S. 2006. Evaluation of herbs as potential alternatives for bear bile and rhino horn used in traditional Chinese medicines: chemical and biological analysis. PhD thesis Middlesex University School of Health and Social Sciences
Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer
Dudziec, E., Miah, S., Choudhry, H., Owen, H., Blizard, S., Glover, M., Hamdy, F. and Catto, J. 2011. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer. Clinical Cancer Research. 17 (6), pp. 1287-1296. https://doi.org/10.1158/1078-0432.CCR-10-2017
Cyclin D-1 protein over-expression is not associated with gene amplification in benign and atypical apocrine lesions of the breast
Elayat, Ghada, Selim, Abdel-Ghani A., Gorman, Patricia, Tomlinson, Ian and Wells, Clive A. 2011. Cyclin D-1 protein over-expression is not associated with gene amplification in benign and atypical apocrine lesions of the breast. Pathology - Research and Practice. 207 (2), pp. 75-78. https://doi.org/10.1016/j.prp.2010.06.003
Investigation of the safety and efficacy of Chinese herbs traditionally used to treat inflammatory diseases
Appiah, S., Kokubun, T., Bremner, P., Heinrich, M., Bell, C. and Simmonds, M. 2003. Investigation of the safety and efficacy of Chinese herbs traditionally used to treat inflammatory diseases. 10th Annual Symposium on Complementary Health Care. London, UK 21 - 22 Nov 2003
Herbal alternatives to bear bile: effects of scutellaria baicalensis Georgi on IL-6 promoter and CYP3A4 activities.
Appiah, S., Bremner, P., Kokubun, T., Russell, M., Bell, C., Heinrich, M. and Simmonds, M. 2006. Herbal alternatives to bear bile: effects of scutellaria baicalensis Georgi on IL-6 promoter and CYP3A4 activities. 13th Annual Symposium on Complementary Health Care. Exeter, UK 12 - 14 Dec 2006
Plant substances as alternatives for animal products in traditional medicines.
Bell, C., Simmonds, M., Appiah, S. and Howes, M. 2006. Plant substances as alternatives for animal products in traditional medicines. London Department for the Environment, Food and Rural Affairs.
Cell turnover in apocrine metaplasia and apocrine adenosis of the breast
Elayat, G., Selim, A. and Wells, C. 2010. Cell turnover in apocrine metaplasia and apocrine adenosis of the breast. Annals of Diagnostic Pathology. 14 (1), pp. 1-7. https://doi.org/10.1016/j.anndiagpath.2009.05.001
Low frequency of epigenetic events in urothelial tumours from young patients
Catto, J., Owen, H., Giedl, J., Wild, P., Fine, S., Epstein, J., Humphrey, P., Dehner, L., Amin, M., Blaszyk, H., Hughes, D., Hartmann, A. and Stoehr, R. 2010. Low frequency of epigenetic events in urothelial tumours from young patients. European Urology Supplements. 9 (2), pp. 260-261. https://doi.org/10.1016/S1569-9056(10)60798-1
Low frequency of epigenetic events in urothelial tumors in young patients
Owen, H., Giedl, J., Wild, P., Fine, S., Humphrey, P., Dehner, L., Amin, M., Epstein, J., Blaszyk, H., Hughes, D., Hartmann, A., Stoehr, R. and Catto, J. 2010. Low frequency of epigenetic events in urothelial tumors in young patients. The Journal of Urology. 184 (2), pp. 459-463. https://doi.org/10.1016/j.juro.2010.03.131
Alterations of the cell cycle regulators cyclin D1, cyclin A, p27, p21, p16, and pRb in apocrine metaplasia of the breast
Elayat, G., Selim, A. and Wells, C. 2009. Alterations of the cell cycle regulators cyclin D1, cyclin A, p27, p21, p16, and pRb in apocrine metaplasia of the breast. Breast Journal. 15 (5), pp. 475-482. https://doi.org/10.1111/j.1524-4741.2009.00762.x
Laser modulation of angiogenic factor production by T-lymphocytes.
Agaiby, A., Ghali, L., Wilson, R. and Dyson, M. 2000. Laser modulation of angiogenic factor production by T-lymphocytes. Lasers in surgery and medicine. 26 (4), pp. 357-363. https://doi.org/10.1002/(SICI)1096-9101(2000)26:4<357::AID-LSM3>3.0.CO;2-O
An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients
Harwood, C., Swale, V., Bataille, V., Quinn, A., Ghali, L., Patel, S., Dove-Edwin, I., Cerio, R. and McGregor, J. 2001. An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients. Journal of investigative dermatology. 116 (2), pp. 246-253. https://doi.org/10.1046/j.1523-1747.2001.01233.x
Human β defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions
Chronnell, C., Ghali, L., Ali, R., Quinn, A., Holland, D., Bull, J., Cunliffe, W., McKay, I., Philpott, M. and Müller-Röver, S. 2001. Human β defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions. Journal of investigative dermatology. 117 (5), pp. 1120-1125. https://doi.org/10.1046/j.0022-202x.2001.01569.x
Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus
Jackson, S., Ghali, L., Harwood, C. and Storey, A. 2002. Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus. British journal of cancer. 87 (3), pp. 319-323. https://doi.org/10.1038/sj.bjc.6600431
Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation, proliferation, and keratinization
Bloor, B., Tidman, N., Leigh, I., Odell, E., Dogan, B., Wollina, U., Ghali, L. and Waseem, A. 2003. Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation, proliferation, and keratinization. American Journal of Pathology. 162 (3), pp. 963-975.
The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin
Akgul, B., Garcia-Escudero, R., Ghali, L., Pfister, H., Fuchs, P., Navsaria, H. and Storey, A. 2005. The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin. Cancer Research. 65 (6), pp. 2216-2223. https://doi.org/10.1158/0008-5472.CAN-04-1952
LEKTI demonstrable by immunohistochemistry of the skin: a potential diagnostic skin test for Netherton syndrome.
Ong, C., O'Toole, E., Ghali, L., Malone, M., Smith, V., Callard, R. and Harper, J. 2004. LEKTI demonstrable by immunohistochemistry of the skin: a potential diagnostic skin test for Netherton syndrome. British journal of dermatology. 151 (6), pp. 1253-1257. https://doi.org/10.1111/j.1365-2133.2004.06180.x
Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in high-risk renal transplant recipients: randomized, double-blind, placebo-controlled trial
Brown, V., Atkins, C., Ghali, L., Cerio, R., Harwood, C. and Proby, C. 2005. Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in high-risk renal transplant recipients: randomized, double-blind, placebo-controlled trial. Archives of Dermatology. 141 (8), pp. 985-993.
Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours
Green, J., Ikram, M., Vyas, J., Patel, N., Proby, C., Ghali, L., Leigh, I., O'Toole, E. and Storey, A. 2006. Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours. British journal of cancer. 94 (10), pp. 1446-1451.
Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria.
Leverrier, S., Bergamaschi, D., Ghali, L., Ola, A., Warnes, G., Akgul, B., Blight, K., Garcia-Escudero, R., Penna, A., Eddaoudi, A. and Storey, A. 2007. Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria. Apoptosis: an international journal on programmed cell death. 12 (3), pp. 549-560. https://doi.org/10.1007/s10495-006-0004-1
Role for WNT16B in human epidermal keratinocyte proliferation and differentiation
Teh, M., Blaydon, D., Ghali, L., Briggs, V., Edmunds, S., Pantazi, E., Barnes, M., Leigh, I., Kelsell, D. and Philpott, M. 2007. Role for WNT16B in human epidermal keratinocyte proliferation and differentiation. Journal of Cell Science. 120 (2), pp. 330-339.
Longitudinal muscle shows abnormal relaxation responses to nitric oxide and contains altered levels of NOS1 and elastin in uncomplicated diverticular disease.
Golder, M., Burleigh, D., Ghali, L., Feakins, R., Lunniss, P., Williams, N. and Navsaria, H. 2007. Longitudinal muscle shows abnormal relaxation responses to nitric oxide and contains altered levels of NOS1 and elastin in uncomplicated diverticular disease. Colorectal disease. 9 (3), pp. 218-228.
HPV8 early genes modulate differentiation and cell cycle of primary human adult keratinocytes.
Akgul, B., Ghali, L., Davies, D., Pfister, H., Leigh, I. and Storey, A. 2007. HPV8 early genes modulate differentiation and cell cycle of primary human adult keratinocytes. Clinical and experimental dermatology. 16 (7), pp. 590-599.
Granulosa cell survival and proliferation are altered in polycystic ovary syndrome
Das, M., Djahanbakhch, O., Hacihanefioglu, B., Saridogan, E., Ikram, M., Ghali, L., Raveendran, M. and Storey, A. 2008. Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism. 93 (3), pp. 881-887. https://doi.org/10.1210/jc.2007-1650
GLI1 repression of ERK activity correlates with colony formation and impaired migration in human epidermal keratinocytes
Neill, G., Harrison, W., Ikram, M., Williams, T., Bianchi, L., Nadenla, S., Green, J., Ghali, L., Frischauf, A., O'Toole, E., Aberger, F. and Philpott, M. 2008. GLI1 repression of ERK activity correlates with colony formation and impaired migration in human epidermal keratinocytes. Carcinogenesis. 29 (4), pp. 738-746. https://doi.org/10.1093/carcin/bgn037
Gonadotropins and prostate cancer: revisited.
Thwaini, A., Naase, M., Chinegwundon, F., Baithun, S., Ghali, L., Shergill, I. and Iles, R. 2006. Gonadotropins and prostate cancer: revisited. Urologia internationalis. 77 (4), pp. 289-296. https://doi.org/10.1159/000096330
Cell cycle alterations and their relationship to proliferation in apocrine adenosis of the breast
Elayat, G., Selim, A. and Wells, C. 2009. Cell cycle alterations and their relationship to proliferation in apocrine adenosis of the breast. Histopathology. 54 (3), pp. 348-354. https://doi.org/10.1111/j.1365-2559.2009.03223.x
Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo
Owen, H., Ahmed, S. and Farquharson, C. 2009. Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcified Tissue International and Musculoskeletal Research. 85 (4), pp. 326-334. https://doi.org/10.1007/s00223-009-9276-0
Distinct microRNA alterations characterize high- and low-grade bladder cancer
Catto, J., Miah, S., Owen, H., Bryant, H., Myers, K., Dudziec, E., Larré, S., Milo, M., Rehman, I., Rosario, D., Di Martino, E., Knowles, M., Meuth, M., Harris, A. and Hamdy, F. 2009. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Research. 69 (21), pp. 8472-8481. https://doi.org/10.1158/0008-5472.CAN-09-0744
Smooth muscle cholinergic denervation hypersensitivity in diverticular disease.
Ghali, L., Belai, A., Burleigh, D. and Golder, M. 2003. Smooth muscle cholinergic denervation hypersensitivity in diverticular disease. The Lancet. 361 (9373), pp. 1945-1951. https://doi.org/10.1016/S0140-6736(03)13583-0
Epidermal and hair follicle progenitor cells express melanoma-associated chondroitin sulfate proteoglycan core protein
Ghali, L., Wong, S., Tidman, N., Quinn, A., Philpott, M. and Leigh, I. 2004. Epidermal and hair follicle progenitor cells express melanoma-associated chondroitin sulfate proteoglycan core protein. Journal of investigative dermatology. 122 (2), pp. 433-442. https://doi.org/10.1046/j.0022-202X.2004.22207.x
FOXM1 is a downstream target of Gli1 in basal cell carcinomas
Teh, M., Wong, S., Neill, G., Ghali, L., Philpott, M. and Quinn, A. 2002. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Research. 62 (16), pp. 4773-4780.
Loss of protein kinase calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma
Ghali, L., Green, J., Ikram, M. and Neill, G. 2003. Loss of protein kinase calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma. Cancer Research. 63 (15), pp. 4692-4697.
Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes
Owen, H., Roberts, S., Ahmed, S. and Farquharson, C. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism. 294 (6), pp. E1023-E1034. https://doi.org/10.1152/ajpendo.00586.2007
Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1
Roberts, S., Owen, H. and Farquharson, C. 2008. Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1. Biochemical and Biophysical Research Communications. 371 (4), pp. 872-876. https://doi.org/10.1016/j.bbrc.2008.04.163
Non-operative breast pathology: Apocrine lesions
Wells, C. and Elayat, G. 2007. Non-operative breast pathology: Apocrine lesions. Journal of Clinical Pathology. 60 (12), pp. 1313-1320. https://doi.org/10.1136/jcp.2006.040626
The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438
Owen, H., Miner, J., Ahmed, S. and Farquharson, C. 2007. The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Molecular and Cellular Endocrinology. 264 (1-2), pp. 164-70. https://doi.org/10.1016/j.mce.2006.11.006
C-myc oncoprotein expression and gene amplification in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast
Selim, A., Elayat, G., Naase, M. and Wells, C. 2002. C-myc oncoprotein expression and gene amplification in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast. The Breast. 11 (6), pp. 466-472. https://doi.org/10.1054/brst.2002.0474
Expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast
Selim, A., Elayat, G. and Wells, C. 2002. Expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast. Virchows Archiv. 441, p. 449–455. https://doi.org/10.1007/s00428-002-0691-0
Loss of heterozygosity and allelic imbalance in apocrine metaplasia of the breast: Microdissection microsatellite analysis
Selim, A., Ryan, A., Elayat, G. and Wells, C. 2002. Loss of heterozygosity and allelic imbalance in apocrine metaplasia of the breast: Microdissection microsatellite analysis. The Journal of Pathology. 196 (3), pp. 287-291. https://doi.org/10.1002/path.1043
c-erbB2 oncoprotein expression, gene amplification, and chromosome 17 aneusomy in apocrine adenosis of the breast
Selim, A., Elayat, G. and Wells, C. 2000. c-erbB2 oncoprotein expression, gene amplification, and chromosome 17 aneusomy in apocrine adenosis of the breast. The Journal of Pathology. 191 (2), pp. 138-142. https://doi.org/10.1002/(sici)1096-9896(200006)191:2<138::aid-path611>3.0.co;2-j