BRIDELIA SCANDENS WILD. A NEW SOURCE FOR PODOPHYLLOTOXIN PRODUCTION IN VITRO BY FEEDING CONIFERYL ALCOHOL
Objective: In the present study, a new method for the production of anticancerous compound podophyllotoxin (PTOX) was developed for Bridelia scandens Wild. by feeding coniferyl alcohol.
Methods: The production of anticancerous compound PTOX through leaf explant derived calli of B. scandens. Murashige and Skoog (MS) medium fortified with 0.5 mg/l 6-Benzylaminopurine (BAP) and 0.5 mg/l 2,4-D (2,4-Dichlorophenoxyacetic acid) induced luxuriant mass of callus growth. Suspension culture was initiated by sterile MS media fortified with 0.1–1.0 mg/l BAP and 0.1–1.0 mg/l 2,4-D. and growth product was analyzed by the high-pressure liquid chromatography method.
Results: Phytochemical analysis of the B. scandens leaf and leaf calli showed the presence of PTOX at the concentrations of 0.69 and 1.81, respectively. The callus cell suspension was established with the same callogenic media also it is augmented with 10–70 mg/l of coniferyl alcohol to elicit the biosynthesis of PTOX. Successive cultures of the calli suspension yielded stable production of PTOX of 3.91 mg/g dry cell weight at 50 mg/l coniferyl alcohol in the media. The biosynthesis of PTOX was ideal when plant cells were cultivated in the dark with an agitation speed of 100 rpm.
Conclusion: The growth and production of PTOX were found to be better with glucose than with sucrose as the medium carbon source. The harvesting of the secondary metabolite from the in vitro grown leaf calli of B. scandens is a better way to stop the exploitation of medicinal plants.
2. Samant SS, Pant S, Singh M, Lal M, Singh A, Sharma A. Medicinal plants in Himachal Pradesh, Northwestern Himalaya, India. Int J Biodivers Sci Manag 2007;3:234-51.
3. Carlström K, Hedin PJ, Jönsson L, Lerndal T, Lien J, Weitoft T. Endocrine effects of the podophyllotoxin derivative drug CPH 82 (Reumacon) in patients with rheumatoid arthritis. Scand J Rheumatol 2000;29:89-94.
4. Bedows E, Hatfield GM. An Investigation of the antiviral activity of Podophyllum peltatum. J Nat Prod 1982;45:725-9.
5. Syed TA, Cheema KM, Khayyami M, Ahmad SA, Ahmad SH, Ahmad S, et al. Human leukocyte interferon-alpha versus podophyllotoxin in cream for the treatment of genital warts in males. Dermatology 1995;191:129-32.
6. Lassus A. Comparison of podophyllotoxin and podophyllin in treatment of genital warts. Lancet 1987;330:512-3.
7. Ayres DC, Loike JD. Lignans : Chemical, Biological, and Clinical Properties. England: Cambridge University Press; 1990.
8. Wantke F, Fleischl G, Götz M, Jarisch R. Topical podophyllotoxin in psoriasis vulgaris. Dermatology 1993;186:79.
9. Beutner KR. Podophyllotoxin in the Treatment of Genital Warts. Vol. 24. Basel, Switzerland: Karger Publishers; 1996.
10. Wilson J. Treatment of genital warts-What’s the evidence? Int J STD AIDS 2002;13:216-20.
11. Markos AR. The successful treatment of molluscum contagiosum with podophyllotoxin (0.5%) self-application. Int J STD AIDS 2001;12:833.
12. Utsugi T, Shibata J, Sugimoto Y, Aoyagi K, Wierzba K, Kobunai T. Antitumor activity of a novel podophyllotoxin derivative (TOP- 53) against lung cancer and lung metastatic cancer. Cancer Res 1996;56:2809-14.
13. Subrahmanyam D, Renuka B, Rao CV, Sagar PS, Deevi DS, Babu JM. Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents. Bioorg Med Chem Lett 1998;8:1391-96.
14. Giri A, Narasu ML. Production of podophyllotoxin from Podophyllum hexandrum: A potential natural product for clinically useful anticancer drugs. Cytotechnology 2000;34:17-26.
15. Ionkova I, Antonova I, Momekov G, Fuss E. Production of podophyllotoxin in Linum linearifolium in vitro cultures. Pharmacogn Mag 2010;6:180-5.
16. Heyenga AG, Lucas J, Dewick P. Production of tumour-inhibitory lignans in callus cultures of Podophyllum hexandrum. Plant Cell Rep 1990;9:382-5.
17. Chattopadhyay S, Srivastava AK, Bhojwani SS, Bisaria VS. Production of podophyllotoxin by plant cell cultures of Podophyllum hexandrum in bioreactor. J Biosci Bioeng 2002;93:215-20.
18. Ardalani H, Avan A, Ghayour-Mobarhan M. Podophyllotoxin: A novel potential natural anticancer agent. Avicenna J Phytomed 2017;7:285-94.
19. Anbazhagan VR, Ahn CH, Harada E, Kim YS, Choi YE. Podophyllotoxin production via cell and adventitious root cultures of Podophyllum peltatum. In Vitro Cell Dev Biol Plant 2008;44:494-501.
20. Tumova L, Gallova K, Rimakova J. Silybum marianum in vitro. Ceska Slov Farm 2004;53:135-40.
21. Woerdenbag HJ, van Uden W, Frijlink HW, Lerk CF, Pras N, Malingre TM. Increased podophyllotoxin production in Podophyllum hexandrum cell suspension cultures after feeding coniferyl alcohol as a ?-cyclodextrin complex. Plant Cell Rep 1990;9:97-100.
22. Kadkade P. Growth and podophyllotoxin production in callus tissues of Podophyllum peltatum. Plant Sci Lett 1982;25:107-15.
23. George EF, Hall MA, De Klerk GJ. The components of plant tissue culture media II: Organic additions, osmotic and pH effects, and support systems. In: Plant Propagation by Tissue Culture. Dordrecht: Springer Netherlands; 2008.
24. Lila MA. Anthocyanins and human health: An in vitro investigative approach. J Biomed Biotechnol 2004;5:306-13.
25. Smollny T, Wichers H, Kalenberg S, Shahsavari A, Petersen M, Alfermann AW. Accumulation of podophyllotoxin and related lignans in cell suspension cultures of Linum album. Phytochemistry 1998;48:975-9.
26. van Uden W, Pras N, Malingré TM. On the improvement of the podophyllotoxin production by phenylpropanoid precursor feeding to cell cultures of Podophyllum hexandrum Royle. Plant Cell Tissue Organ Cult 1990;23:217-24.
27. Xia ZQ, Costa MA, Proctor J, Davin LB, Lewis NG. Dirigent-mediated podophyllotoxin biosynthesis in Linum flavum and Podophyllum peltatum. Phytochemistry 2000;55:537-49.
28. Pelter A. Lignans: Some properties and syntheses. Recent Adv Phytochem 1986;20:201-41.
29. Freudenberg K. Lignin: Its constitution and formation from p-hydroxycinnamyl alcohols: Lignin is duplicated by dehydrogenation of these alcohols; intermediates explain formation and structure. Science 1965;148:595-600.
30. Ahmad R, Sharma VK, Rai AK, Shivananda RD, Shivananda BG. Production of lignans in callus culture of Podophyllum hexandrum. Trop J Pharm Res 2007;6:803-8.
31. Bedir E, Khan I, Moraes RM. Bioprospecting for podophyllotoxin. In: Janick J, Whipkey A, editors. Trends in New Crops and New Uses. Alexandria, VA, USA: ASHS Press; 2002. p. 545-9.
32. Wink M, Alfermann AW, Franke R, Wetterauer B, Distl M, Windhövel J. Sustainable bioproduction of phytochemicals by plant in vitro cultures: Anticancer agents. Plant Genet Resour 2005;3:90-100.
33. Baldi A, Srivastava AK, Bisaria VS. Improved podophyllotoxin production by transformed cultures of Linum album. Biotechnol J 2008;3:1256-63.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.