Anticancer, antioxidant properties and phenolic, flavonoid composition of Heracleum platytaenium plant methanolic extracts

Abstract

Heracleum platytaenium is an edible herb and strongly aromatic plant that is endemic to Turkey. Although, a number of studies have been conducted on the components and composition of essential oils of the different parts of this species, its antioxidant, antiproliferative and /or cytotoxic proporties have never been explored. The present study aimed to evaluate total phenolic content (TPC), total flavonoid content (TFC), the antioxidant activity and anticancer properties of the methanolic extracts of H. platytaenium. The results showed that the total phenolic and flavonoid contents were found to be higher in the methanolic extracts from the flowers of the plant. The methanolic flower extract of H. platytaenium scavenged about 86% and stem extract of H. platytaenium scavenged about 83% of free DPPH radicals. The best inhibitory profile for GST was observed with the methanolic extract of the plant from flowers. In addition, the methanol extract of H. platytaenium from the stem increased GPx activity with the 1.25 mg/mg plant extract. The maximum dose of the flower and stem extracts of the plant inhibited 10 % and 8% CAT activity. Then, MTT assay was used for the study of the cytotoxic effect of the plant extracts. Both methanolic flower and stem extract of H. platytaenium showed moderate anticancer effect on T47-D cell lines, but no cytotoxic effect was observed on MDA-MB-231 cells. In conclusion, methanolic extracts of H. platytaenium flower and stem showed apparent antioxidant and cytotoxic effects leading the way for their potential use as food additives to help to fight against the growth and spreading of cancerous cells. However, for a definitive conclusion, further studies on other cell lines as well as animal models and subsequent clinical studies are warranted.

Keywords

• Antioxidant enzymes
• breast cancer cell line
• cytotoxicity
• flavonoids
• Heracleum platytaenium
• phenolics

References

1. [1] Bahadori MB, Dinparast L, Zengin G. The Genus Heracleum: A comprehensive-review on its phytochemistry, pharmacology, and ethnobotanical values as a useful herb. Compr Rev Food Sci Food Saf. 2016; 15(6): 1018-1039.
2. [2] Pimenov MG, Leonov MV. The asian umbelliferae biodiversity database (ASIUM) with particular reference to south-west asian taxa. Turk J Bot. 2004; 28: 139–145.
3. [3] Taniguchi M, Yokota O, Shibano M, Wang N-H, Baba K. Four coumarins from Heracleum yunngningense. Chem Pharm Bull (Tokyo). 2005; 53(6): 701–704.
4. [4] Souri E, Farsam H, Sarkheil P, Ebadi F. Antioxidant activity of some furanocoumarins isolated from Heracleum persicum. Pharm Biol. 2004; 42(6): 396-399.
5. [5] Dincel D. M.Sc. Thesis. Isolation of secondary metabolites of Prangos ilanae and Heracleum platytaenium plants, investigation of their antioxidant and anticholinesterase activities. Department of Chemistry, Faculty of Science, Istanbul Technical University, İstanbul, Turkey, 2011.
6. [6] Kilic CS, Demirci B, Coskun M, Baser KHC. Chemical composition of Heracleum platytaenium Boiss. (Apiaceae) essential oil from Turkey. Nat Vol Essent Oils. 2017; 3(4): 13-23.
7. [7] Aydin E, Turkez E, Taşdemir S. Anticancer and antioxidant properties of terpinolene in rat brain cells. Arh Hig Rada Toksikol. 2013; 64(3): 415-424.
8. [8] Stefano VD, Pitonzo R, Schillaci D. Antimicrobial and antiproliferative activity of Athamanta sicula L. (Apiaceae). Pharmacogn Mag. 2011; 7(25): 31-44.

9. [9] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7–30.
10. [10] Cancer Research UK report 2013. http://cancerhelp.cancerresearchuk.org/aboutcancer/treatment/cancerdrugs/sideeffect.
11. [11] Banerji S, Cibulskis KC, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012; 486(7403): 405–409.
12. [12] Ozmen V. Breast Cancer in Turkey: Clinical and histopathological characteristics (Analysis of 13.240 Patients). J Breast Health. 2014; 10(2): 98–105.
13. [13] Safarzadeh E, Shotorbani SS, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 2014; 4(1): 421–427.
14. [14] Raguz S, Yague E. Resistance to chemotherapy: New treatments and novel insights into an old problem. Br J Cancer. 2008; 99(3): 387–391.
15. [15] Liu RH. Potential synergy of chemicals in cancer prevention. J Nutr. 2004; 22: 3479-3485.
16. [16] Udenigwe CC, Ata A, Samarasekera R. Glutathione s-transferase inhibiting chemical constituents of Caesalpinia bonduc. Chem Pharm Bull (Tokyo). 2007; 55(3): 442-445.
17. [17] Prasad KN, Cole WC, Kumar B, Prasad KC. Pros and cons of antioxidant use during radiation therapy. Cancer Treat Rev. 2002; 28(2): 79-91.
18. [18] Ata A, Bosch SAVD, Harwanik DJ, Pidwinski GE. Glutathione s-transferase and acetylcholinesterase inhibiting natural products from medicinally important plants. Pure Appl Chem. 2007; 79(12): 2269-2276.
19. [19] Ghasemzadeh A, Ghasemzadeh N. Flavonoids and phenolic acids: Role and biochemical activity in plants and human. J Med Plants Res. 2011; 5(31): 6697-6703.
20. [20] Lin D, Xiao M, Zhao J, Li Z, Xing B, Li X, Kong M, Li, Zhang Q, Liu Y. An overview of plant phenolic compounds and their importance in human nutrition and management of type 2 diabetes. Molecules. 2016; 21(10): 1374.
21. [21] Ravishankar D, Rajora AK, Greco F, Osborn HMI. Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol. 2013; 45(12): 2821–2283.
22. [22] Mannervik B, Danielson UH. Glutathione transferases-structure and catalytic activity. CRC Crit Rev Biochem. 1998; 23: 283.
23. [23] Ramsay EE, Dilda PJ. Glutathione s-conjugates as prodrugs to target drug-resistant tumors. Front Pharmacol. 2014; 5: 181.
24. [24] Hu YJ, Diamond AM. Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res. 2003; 63(12): 3347-3351.
25. [25] Ratnasinghe D, Tangrea JA, Andersen MR, Barrett MJ, Virtamo J, Taylor PR, Albanes D. Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res. 2000; 60(22): 6381-6383.
26. [26] Glorieux C, Calderon PB. Catalase, a remarkable enzyme: Targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol Chem. 2017; 398(10): 1095-1108.
27. [27] Sakanaka S, Tachibana Y, Okada Y. Preparation and antioxidant properties of extracts of Japanese persimmon leaf tea (kakinoha-cha). Food Chem. 2005; 89(4): 569–575.
28. [28] Erkan N, Ayranci G, Ayranci E. Antioxidant activities of rosemary (Rosmarinus Officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol. Food Chem. 2008; 110(1): 76–82.
29. [29] Lumachi F, Brunello A, Maruzzo M, Basso U, Basso S. Treatment of estrogen receptor-positive breast cancer. Curr Med Chem. 2013; 20(5): 596-604.
30. [30] Slinkard K, Singleton VL. Total phenol analyses: Automation and comparison with manual methods. Am J Enol Vitic. 1977; 28: 49-55.
31. [31] Simone CB, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival. Altern Ther Health Med. 2007; 13(1): 22-28.
32. [32] Sharma OP, Bhat TK. DPPH antioxidant assay revisited. Food Chem. 2009; 113: 1202–1205.
33. [33] Habig WH, Pabst MJ, Jakoby WB. Glutathione-s-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974; 249: 7130–7139.
34. [34] Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967; 70(1): 158-169.
35. [35] Aebi H. Catalase in vitro. Methods Enzymol. 1984; 105: 121-126.
36. [36] Sriwiriyajan S, Ninpesh T, Sukpondma Y, Nasomyon T, Graidist P. Cytotoxicity screening of plants of genus Piper in breast cancer cell lines. Trop J Pharm Res. 2014; 13: 921–928.