Identification of Lilium ledebourii antiproliferative compounds against skin, bone and oral cancer cells

Document Type : Original Research Article

Authors

1 Department of Plant Biotechnology, Faculty of Agriculture, University of Guilan, Rasht, Iran

2 Department of Biochemistry, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran

3 Phytochemistry Group, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

Abstract

Objective: This study aimed at the evaluation of anti antiproliferative activity of Lonicera nummularifolia, Lilium ledebourii, Campsis radicans and Parthenocissus quinquefolia extracts.
Materials and Methods: The extract was taken from the fresh leaves and bulbs of the plants by maceration method in the dark. After separating the solvent, the remaining dry matter was added to the culture medium containing G292, A431 and KB cancer and HGF-1 normal cells. Cytotoxicity tests, as well as cell cycle and apoptosis tests were performed on cells treated with dry substances and untreated cells. Finally, the most effective extract was separated into fractions by preparative HPLC and the effective fraction was characterized by Triple-Quad LC/MS connected to the UHPLC system.
Results: All extracts significantly enhanced cell death rate in the three cancer cell lines more than the HGF-1 line. The Methanolic extract of L. ledebourii bulbs exhibited considerable efficacy on apoptosis induction in the cancer cell lines. It seems that the mode of action for L. ledebourii methanolic extract is mediated through increased BID/MAPK14 expression and decreased MDM2/BCL2/MYC expression, which led to activation of the p53 protein-induced apoptosis. It was also determined that the effective fraction of L. ledebourii methanolic extract consists of substances such as caffeic acid, ferulic acid, coumarin acid, catechin and apigenin.
Conclusion: Overall, the findings suggest that L. ledebourii is a promising source of bioactive compounds with anticancer properties.

Keywords

Main Subjects


Ackermann T, Tardito S. 2019. Cell culture
medium formulation and its implications in
cancer metabolism. Trends Cancer, 5: 329-
332.
Anwar T, Arellano‐Garcia C, Ropa JP, Chen
Y, Kim HS, Yoon E, Grigsby SM, Basrur
V, Nesvizhskii AI, Muntean AG, Gonzalez
ME, Kidwell KM, Nikolovska-Coleska Z,
Kleer CG. 2018. p38 mediated
phosphorylation at T367 induces EZH2
cytoplasmic localization to promote breast
cancer metastasis. Nat Commun, 9: 2801.
Billen L, Shamas-Din A, Andrews D. 2008.
Bid: a Bax-like BH3 protein. Oncogene,
27: S93-S104.
Chen H, Liu H, Qing G. 2018. Targeting
oncogenic Myc as a strategy for cancer
treatment. Sig Transduct Target Ther, 3: 5.
Chikara S, Nagaprashantha LD, Singhal J,
Horne D, Awasthi S, Singhal SS. 2018.
Oxidative stress and dietary
phytochemicals: role in cancer
chemoprevention and treatment. Cancer
Lett, 413: 122-134.
D'Arcy MS. 2019. Cell death: a review of the
major forms of apoptosis, necrosis and
autophagy. Cell Biol Int, 43: 582-592.
Dhillon A, Hagan S, Rath O, Kolch W. 2007.
MAP kinase signalling pathways in cancer
Oncogene, 26: 3279-3290.
Elmore S. 2007. Apoptosis: a review of
programmed cell death. Toxicol Pathol, 35:
495-516.
Faisal S, Perveen A, Khan ZU, Sardar AA,
Shaheen S, Manzoor A. 2018.
Phytochemical screening and antioxidant
potential of Parthenocissus quinquefolia
(L.) planch extracts of bark and stem. Pak J
Pharm Sci, 31: 1813-1816.
Farboodniay Jahromi MA, Emami A, Nazeri
R, Pirbonyeh N. 2020. Antibacterial and
antioxidant activity of extract and fractions
of Lonicera nummularifolia Jaub & Spach.
Trends Pharmacol Sci, 6: 131-142.
Florento L, Matias R, Tuaño E, Santiago K,
Dela Cruz F, Tuazon A. 2012. Comparison
of cytotoxic activity of anticancer drugs
against various human tumor cell lines
using in vitro cell-based approach. Int J
Biomed Sci, 8: 76-80.
Greenwell M, Rahman PK. 2015. Medicinal
Plants: Their use in anticancer treatment.
Int J Pharm Sci Res, 6: 4103-4112.
Gupta J, del Barco Barrantes I, Igea A,
Sakellariou S, Pateras IS, Gorgoulis VG,
Nebreda AR. 2014. Dual function of p38α
MAPK in colon cancer: suppression of
colitis‐associated tumor initiation but
requirement for cancer cell survival. Cancer
Cell, 25: 484‐500.
Islam M, Jannat T, Kuddu, MR, Rashid MA,
Haque MR. 2019. In vitro and in vivo
evaluation of pharmacological potentials of
Campsis radicans L. Clin Phytosci, 5: 42.
Livak KJ, Schmittgen TD. 2001. Analysis of
relative gene expression data using realtime quantitative PCR and the 2−ΔΔCT
method. Methods, 25: 402-408.
Partovi et al.
AJP, Vol. 13, No. 6, Nov-Dec 2023 638
Luo J, Li L, Kong L. 2012. Preparative
separation of phenylpropenoid glycerides
from the bulbs of Lilium lancifolium by
high-speed counter-current chromatography
and evaluation of their antioxidant
activities. Food Chem, 131: 1056-1062.
Mahdinezhad N, Fakheri BA, Ghanbari S.
2018. Phytochemical compounds of Lilium
ledebourii bioss using bulb explants.
Bangladesh J Bot, 4: 911-920.
Mantovani F, Collavin L, Del Sal G. 2019.
Mutant p53 as a guardian of the cancer cell.
Cell Death Differ, 26: 199-212.
Mishra A, Behura A, Mawatwal S,
Kumar A, Naik L, Mohanty
SS, Manna D, Dokania
P, Mishra A, Patra SK, Dhiman R. 2019.
Structure-function and application of plant
lectins in disease biology and immunity.
Food Chem Toxicol, 134: 110827.
Munafo JP, Gianfagna TJ. 2015. Quantitative
analysis of phenylpropanoid glycerol
glucosides in different organs of Easter Lily
(Lilium longiflorum Thunb.). J Agric Food
Chem, 63: 4836-4842.
Phesse T, Myant K, Cole A, Ridgway RA,
Pearson H, Muncan V, van den Brink GR,
Vousden KH, Sears R, Vassilev LT, Clarke
AR, Sansom OJ. 2014. Endogenous c-Myc
is essential for p53-induced apoptosis in
response to DNA damage in vivo. Cell
Death Differ, 21: 956-966.
Pucci C, Martinelli C, Ciofani G. 2019.
Innovative approaches for cancer treatment:
Current perspectives and new challenges.
Ecancermedicalscience, 13: 961.
Renehan AG, Booth C, Potten CS. 2001. What
is apoptosis, and why is it important? BMJ,
322: 1536-1538.
Rezadoost MH, Ghasempour A, Hasani
Komleh H. 2019a. Apoptosis induction by
Calystegia Sepium HPLC fraction can be
via dual targeting of MDM2 and BCL-2 in
cancer cells. BMMJ, 5: 83-95.
Rezadoost MH, Kumleh HH, Ghasempour A.
2019b. Cytotoxicity and apoptosis
induction in breast cancer, skin cancer and
glioblastoma cells by plant extracts. Mol
Biol Rep, 46: 5131-5142.
Seca AML, Pinto DCGA. 2018. Plant
secondary metabolites as anticancer agents:
successes in clinical trials and therapeutic
application. Int J Mol Sci, 19: 263.
Shokrollahi S, Heshmati G, Yosef Zadeh H.
2018. Study the phenolic compounds and
antioxidant activity of the extract Lily
(Lilium ledebourii (Baker) Boiss). J Fasa
Univ Med Sci, 8: 727-734.
Siegel RL, Miller KD, Jemal A. 2020. Cancer
statistics, 2020. CA Cancer J Clin, 70: 7-
30.
Wagner EF, Nebreda AR. 2009. Signal
integration by JNK and p38 MAPK
pathways in cancer development. Nat Rev
Cancer, 9: 537‐549.
Wahle KW, Brown I, Rotondo D, Heys SD.
2010. Plant phenolics in the prevention and
treatment of cancer. Adv Exp Med Biol,
698: 36-51.
Zhao K, Xiao Z, Zeng J, Xie H. 2021. Effects
of different storage conditions on the
browning degree, PPO activity, and content
of chemical components in fresh Lilium
bulbs (Lilium brownie F.E.Brown var.
viridulum Baker.). Agriculture, 11: 184.