Acorus calamus bitki ekstraktının prostat kanser hücre kültürü üzerine etkileri

Year 2018, Volume: 2 Issue: 1, 46 - 51, 01.05.2018

Halit Buğra Koca , Tülay Köken , Mete Özkurt Gökhan Kuş , Selda Kabadere Nilüfer Erkasap Oğuzhan Koca , Ömer Çolak

https://doi.org/10.30616/ajb.391985

Cited By: 7

Abstract

Batılı ülkelerde
erkekler arasında prostat kanseri en sık tanısı koulan kanser türüdür ve
erkeklerde kanser nedeniyle ölümde ikinci sırada yer almaktadır. Prostat
kanserinde vasküler endotelyal büyüme faktör-A’nın (VEGF-A) tek başına en
önemli anjiogenik faktör olduğu düşünülmektedir. Apoptotik süreçte yer alan
poli-(ADP-riboz) polimeraz’ın (PARP) yıkılımı apoptotik süreç markırı olarak
kullanılmaktadır. Acorus calamus’un
anti-kanserojen etkisi ile birlikte çeşitli tıbbi özelliklere sahip olduğu uzun
yıllardır özellikle Asya’da kabul edilmektedir. Çalışmamızda A. calamus kökünün etanolik ekstraktının
insan prostat kanser LNCaP hücre dizisinde hücre çoğalmasına, anjiogeneze ve
apoptozise olası etkileri in vitro
ortamda çalışıldı. Hücreler 24 ve 48 saat boyunca çeşitli ekstrakt
konsantrasyonlarıyla muamele edildi. Bu konsantrasyonlardaki ekstraktlar 24 ve
48 saatte LNCaP hücre yaşayabilirliğini kontrolle karşılaştırıldığında doza ve
zamana bağlı olarak %44’lere kadar azalttı. Bölünmüş PARP, VEGF-A proteini ve
gen ekspresyon miktarlarında 24 ve 48 saat sonra belirgin değişiklikler
gözlemlendi. Bu çalışma A.calamus
kökünün etanolik ekstraktının zaman ve doz bağımlı olarak güçlü bir
anti-kanser, anti-anjiogenik ve apoptotik etkileri olabileceğini ortaya
koymaktadır.

Keywords

LNCaP, Acorus calamus, anti-kanser, anti-anjiogenik, apoptotik

Effects of Acorus calamus plant extract on prostate cancer cell culture

Abstract

In western countries,
prostate cancer is the most frequently diagnosed cancer and the second most
common cause of death from cancer in men. Vascular endothelial growth factor-A
(VEGF-A), thought to be the single most important angiogenic factor in prostat
cancer. Poly-(ADP-ribose) polymerase (PARP) involved in apoptotic process and
cleavage of PARP serves as a marker of cells undergoing apoptosis. Acorus calamus have long been considered
to have anti-carcinogenic and medicinal properties especially in Asia. We
examined whether ethanolic extract of A.
calamus root affects the survival of prostate cancer LNCaP cells and
induces apoptosis and angiogenesis of these cells in vitro. Cells were incubated during 24 and 48 hours with various
doses of extract. Extract with these concentrations reduced the number of LNCaP
living cells up to 44 % as compared to the control at dose and time dependent
manner at 24 and 48 hours. Significantly alterations were observed at cleaved
PARP, VEGF-A protein and gene expression amounts after 24 and 48 hours. The
present study reveals the possibility that ethanolic extract of A. calamus root posseses a dose and time
dependent anticancer, apoptotic and anti-angiogenic properties.

Keywords

LNCaP, acorus calamus, anti-cancer, anti-angiogenic, apoptotic

References

• Acuna UM, Atha DE, Ma J, Nee MH, Kennelly EJ (2002). Antioxidant capacities of ten edible North American plants. Phytother Res 16(1): 63-65.
• Bains JS, Dhuna V, Singh J, Kamboj SS, Nijjar KK, Agrewala JN. (2005). Novel lectins from rhizomes of teo Acorus species with mitogenic activity and inhibitory potential towards murine cancer cell lines. Int Immunopharmacol 5(9): 1470-8.
• Bisht VK, Negi JS, Bhandari AK, Sundriyal RC (2011). Anti-cancerous Plants of Uttarakhand Himalaya: A Review. International Journal of Cancer Research 7: 192-208.
• Bohm I, Schild H (2003). Apoptosis: the complex scenario for a silent cell death. Mol Imaging Biol 5: 2-14.
• Brock WA, Milas L, Bergh S, Lo R, Szabó C, Mason KA (2004). Radiosensitization of human and rodent cell lines by INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase. Cancer Lett 205(2): 155-160.
• Devi SA, Ganjewala D (2009). Antimicrobial activity of Acorus calamus (L.) rhizome and leaf extract. Acta Biologica Szegediensis 53(1): 45-49.
• Dungey FA, Caldecott KW, Chalmers AJ (2009). Enhanced radiosensitization of human glioma cells by combining inhibition of poly(ADP-ribose) polymerase with inhibition of heat shock protein 90. Mol Cancer Ther 8(8): 2243-2254.
• Ferrara N, Gerber HP, LeCouter J (2003). The biology of VEGF and its receptors. Nat Med 9: 669-76.
• Folkman J (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182-1186.
• Gerald WP, Poettler M, Unseld M, Zielinski CC (2012). Angiogenesis in cancer: anti-VEGF escape mechanisms. Transl Lung Cancer Res 1(1): 14-25.
• Jesse W-H.L,Verdaras JC (2009). Drug discovery and natural products: end of an era or an endless frontier? Science 325: 161-165. Joshi RK (2016). Acorus calamus Linn.: phytoconstituents and bactericidal property. World J Microbiol Biotechnol 32(10): 164.
• Kevekordes S, Spielberger J, Burghaus CM, Birkenkamp P, Zietz B, Paufler P, Diez M, Bolten C, Dunkelberg H (2001). Micronucleus formation in human lymphocytes and in the metabolically competent human hepatoma cell line Hep-G2: results with 15 naturally occuring substances. Anticancer Res 21(1A): 461-469.
• Kim H, Tan TH, Lee SG (2009). Anti-inflammatory activity of a water extract of Acorus calamus L. leaves on keratinocyte HaCaT cells. J Ethnopharmacol 122(1): 149-156.
• Kim SH, Kim EC, Kim WJ, Lee MH, Kim SY, Kim TJ (2016). Coptis japonica Makino extract suppresses angiogenesis through regulation of cell cycle-related proteins, Bioscience, Biotechnology, and Biochemistry 80(6): 1095-106.
• Kitagawa Y, Dai J, Zhang J, Keller JM, Nor J, Yao Z, Keller ET (2005). Vascular Endothelial Growth Factor Contributes to Prostate Cancer–Mediated Osteoblastic Activity. Cancer Res 65(23): 10921-10929.
• Lee M, Hwang JT, Yun H, Kim EJ, Kim MJ, Kim SS, Ha J (2006). Critical roles of AMP-activated protein kinase in the carcinogenic metal-induced expression of VEGF and HIF-1 proteins in DU145 prostate carcinoma. Biochemical Pharmacology 72(1): 91–103.
• Liu L, Wang J, Shi L, Zhang W, Du X, Wang Z, Zhang Y (2013). Beta-Asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression. Phytomedicine 20: 512-520.
• Mahapatra DK, Bharti SK, Asati V (2015). Anti-cancer chalcones: Structural and molecular target perspectives. Eur J Med Chem 98: 69–114.
• Nicholson B, Theodorescu D (2004). Angiogenesis and Prostate Cancer Tumor Growth. Journal of Cellular Biochemistry 91: 125–150.
• Pandit S, Mukherjee PK, Ponnusankar S, Venkatesh M, Srikanth N (2011).
• Metabolism mediated interaction of α-asarone and Acorus calamus with CYP3A4 and CYP2D6. Fitoterapia 82(3): 369-374.
• Penning TD, Zhu GD, Gandhi VB, Gong JC, Liu XS, Shi Y, Klinghofer V, Johnson EF, Donawho CK, Frost DJ, Bontcheva-Diaz V, Bouska JJ Osterling DJ, Olson AM, Marsh KC, Luo Y. Giranda VL (2009). Discovery of the poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4- carboxamide (ABT-888) for the treatment of cancer. J Med Chem 52: 514-523.
• Raja AE, Vijayalakshmi M, Devalarao G (2009). Acorus calamus Linn.: Chemistry and Biology. Research Journal of Pharmacy and Technology 2(2): 256-261. Shah AJ, Gilani AU (2010). Bronchodilatory effect of Acorus calamus (Linn.) is mediated through multiple pathways. J Ethnopharmacol 131(2): 471-477.
• Shukla PK, Khanna VK, Ali MM, Maurya R, Khan MY, Srimal RC (2006). Neuroprotective effect of Acorus calamus against middle cerebral artery occlusion-induced ischaemia in rat. Hum Exp Toxicol 25(4): 187-94.
• Wei L, Lin J, Xu W, Hong Z, Liu X, Peng J (2011). Inhibition of tumor angiogenesis by Scutellaria barbata D. Don via suppressing proliferation, migration and tube formation of endothelial cells and downregulation of the expression of VEGF-A in cancer cells. Journal of Medicinal Plants Research 5(14): 3260-3268.
• Wu J, Zhang XX, Sun QM, Chen M, Liu SL, Zhang X, Zhou JY, Zou X (2015). β-Asarone inhibits gastric cancer cell proliferation. Oncol Rep 34(6): 3043-50. Wu Q, Kang Y, Zhang H, Wang H, Liu Y, Wang J (2014). The anticancer effects of hispolon on lung cancer cells. Biochemical and Biophysical Research Communications 453: 385–391.
• Zhao L, Wen Q, Yang G, Huang Z, Shen T, Li H, Ren D (2016). Apoptosis induction of dehydrobruceine B on two kinds of human lung cancer cell lines through mitochondrial-dependent pathway. Phytomedicine 23(2): 114-122.
• Zou X, Liu SL, Zhou JY, Wu J, Ling BF, Wang RP (2012). Beta-asarone induces LoVo colon cancer cell apoptosis by up-regulation of caspases through a mitochondrial pathway in vitro and in vivo. Asian Pac J Cancer Prev 13(10): 5291-8.
• Zuba D, Byrska B (2012). Alpha- and beta-asarone in herbal medicinal products. A case study. Forensic Sci Int 223(1-3): 5-9.