Cytotoxic effects of hydroalcoholic extract of Cuscuta chinensis on PC3 and MCF7 cancer cell lines

Document Type : Original Research Article

Authors

1 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan Iran

2 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

3 Department of pharmacognosy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

4 Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan,Iran

5 Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

6 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran .

7 Natural Resources Department, Hamadan Agricultural and Natural Resources Research and Education Center, AREEO, Hamadan, Iran

Abstract

Objective: Chemoprevention of cancer by application of natural phytochemical compounds has been used to prevent, delay or suppress cancer progression. Cuscuta chinensis a traditional Iranian medicinal herb, has biological properties including anticancer, anti-aging, immuno-stimulatory and antioxidant effects. In this study, anti-proliferative effects of hydroalcoholic extract of C. chinensis on prostate (PC3) and breast (MCF7) cancer cell lines were investigated.
Materials and Methods: In the current study, we investigated treatment of PC3 cells with different concentrations of C. chinensis (0, 100, 200, 300, 400, and 500 µg/ml) for 24 and 48 hr; also, MCF7 cells were treated with various concentrations (0-600 µg/ml) of C. chinensis for 48 and 72 hr and cell viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. mRNA expression of BCL2 Associated X (Bax), B-cell lymphoma 2 (Bcl2), Cysteine-aspartic proteases (Caspase3) and Phosphatase and tensin homolog (PTEN) were analyzed by quantitative real-time PCR. Annexin V/PI staining and lactate dehydrogenase (LDH) cytotoxicity assay were used to detect apoptosis.
Results: C. chinensis decreased PC3 and MCF7 cells viability in a dose- and time-dependent manner (p BAX/Bcl2 ratio, Caspase3 and PTEN increased in C. chinensis-treated cells compared to the control group. C. chinensis induced apoptosis (p <0.001) and LDH activity (p Conclusion: Our findings suggest that C. chinensis extract is able to inhibit proliferation and induce apoptosis in PC3 and MCF7 cell lines. Therefore, C. chinensis extract exerts antitumor activity against cancer cells. 

Keywords


Amidi N, Moradkhani S, Sedaghat M,
Khiripour N, Larki-Harchegani A,
Zadkhosh N, Mirhoseini M, Ranjbar A.
2016. Effect of green tea on inflammation
and oxidative stress in cisplatin-induced
experimental liver function. J HerbMed
Pharmacol, 5: 99-102.
Behzad S, Pirani A, Mosaddegh M. 2014.
Cytotoxic activity of some medicinal
plants from Hamedan district of Iran.
Iran J Pharm Res, 13: 199-205.
Bao X, Wang Z, Fang J, Li X. 2002. Structural
features of an immunostimulating and
antioxidant acidic polysaccharide from the
seeds of Cuscuta chinensis. Planta Med, 68:
237-243.
Chan SH, Leu WJ, Hsu LC, Chang HS, Hwang
TL, Chen IS, Chen CS,Guh JH. 2013.
Reevesioside F induces potent and efficient
anti-proliferative and apoptotic activities
through Na+/K+-ATPase α 3 subunitinvolved mitochondrial stress and
amplification of caspase cascades. Biochem
pharmacol, 86: 1564-1575.
Cory S, Adams JM. 2002. The Bcl2 family:
regulators of the cellular life-or-death
switch. Nat Rev Cancer, 2: 647-656.
Ghazanfari T, Naseri M, Shams J, Rahmati B.
2013.Cytotoxic effects of Cuscuta extract on
human cancer cell lines. Food Agric
Immunol, 24: 87-94.
Hsieh TC, Lu X, Guo J, Xiong W, Kunicki J,
Darzynkiewicz Z. 2002. Effects of herbal
preparation Equiguard™ on hormoneresponsive and hormone-refractory prostate
carcinoma cells: Mechanistic studies. Int J
Oncol, 20: 681-689.
Cuscuta chinensis effect on human cancer cell lines
AJP, Vol. 11, No. 3, May-Jun 2021 267
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun
MJ. 2009. Cancer statistics, 2009. CA
Cancer J Clin, 59: 225-249.
Jian-Hui L, Bo J, Yong-Ming B, Li-Jia A. 2003.
Effect of Cuscuta chinensis glycoside on the
neuronal differentiation of rat
pheochromocytoma PC12 cells. ISDN, 21:
277-281.
Kang Y. 2009. Analysis of cancer stem cell
metastasis in xenograft animal models.
Methods Mol Biol, 568: 7-19.
Karimi DF, Amini R, Saidijam M, Pourjafar M,
Saki S, Najafi R. 2018. Zerumbone inhibits
epithelial‐mesenchymal transition and
cancer stem cells properties by inhibiting the
β‐catenin pathway through miR‐200c. J Cell
Physiol, 233: 9538-9547.
Karimi Dermani F, Saidijam M, Amini R,
Mahdavinezhad A, Heydari K, Najafi R.
2017. Resveratrol inhibits proliferation,
invasion, and epithelial–mesenchymal
transition by increasing miR‐200c
expression in HCT‐116 colorectal cancer
cells. J Cell Biochem, 118:1547-1555.
Kerr JF, Wyllie AH, Currie AR. 1972.
Apoptosis: a basic biological phenomenon
with wide-ranging implications in tissue
kinetics. Br JCancer, 26: 239-257.
Lewandowska U, Owczarek K, Szewczyk K,
Podsędek A, Koziołkiewicz M, Hrabec E.
2014. Influence of polyphenol extract from
evening primrose (Oenothera paradoxa)
seeds on human prostate and breast cancer
cell lines. Postepy Hig Med Dosw, 6: 110-
118.
Livak KJ, Schmittgen TD. 2001. Analysis of
relative gene expression data using real-time
quantitative PCR and the 2− ΔΔCT method.
Methods, 25: 402-408.
Li Z, Wang L, Zhang W, Fu Y, Zhao H, Hu Y,
Prins PB, Zha X. 2007. Restoring Ecadherin-mediated cell–cell adhesion
increases PTEN protein level and stability in
human breast. Biochem Bioph Res Co, 363:
165-170.
Martin SJ, Reutelingsperger CP, McGahon AJ,
Rader JA, Van Schie RC, LaFace DM,
Green DR. 1995. Early redistribution of
plasma membrane phosphatidylserine is a
general feature of apoptosis regardless of the
initiating stimulus: inhibition by
overexpression of Bcl-2 and Abl. J Exp
Med, 182: 1545-1556.
Nisa M, Akbar S, Tariq M, Hussain Z. 1986.
Effect of Cuscuta chinensis water extract on
7, 12-dimethylbenz [a] anthracene-induced
skin papillomas and carcinomas in mice. J
Ethnopharmacol, 18: 21-31.
Redig AJ, McAllister SS. 2013. Breast cancer
as a systemic disease: a view of metastasis.
J Intern Med, 274: 113-126.
Smith SM, Wunder MB, Norris DA, Shellman
YG. 2011. A simple protocol for using a
LDH-based cytotoxicity assay to assess the
effects of death and growth inhibition at the
same time. PloS one, 6: e26908.
Sporn MB, Suh N. 2000. Chemoprevention of
cancer. Carcinogenesis, 21:525-530.
Sepehr MF, Jameie SB, Hajijafari B. 2011. The
Cuscuta kotschyana effects on breast cancer
cells line MCF7. J Med Plants Res, 5: 6344-
6351.
Sundquist T, Moravec R, Niles A, O’Brien M,
Riss T. 2006. Timing your apoptosis assays.
Cell Notes, 16:18-21.
Shu J, He Y, Lv X, Zhao J, Zhao J, Shen Y, Ye
GR, Wang LX. 2009. Effect of curcumin on
the proliferation and apoptosis ofhepatic
stellate cells. Braz J Med Biol Res, 42: 1173-
1178.
un X-M, MacFarlane M, Zhuang J, Wolf BB,
Green DR, Cohen GM. 1999. Distinct
caspase cascades are initiated in receptormediated and chemical-induced apoptosis.
J Biol Chem, 274: 5053-5060.
Tryggvadóttir L, Gislum M, Bray F, Klint Å,
Hakulinen T, Storm HH, Engholm G. 2002.
Trends in the survival of patients diagnosed
with breast cancer in the Nordic countries
1964–2003 followed up to the end of 2006.
Acta Oncol, 49: 624-631.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐
TieulentJ, Jemal A. 2015. Global cancer
statistics. CA Cancer J Clin, 65: 87-108.
Umehara K, Nemoto K, Ohkubo T, Miyase T,
Degawa M, Noguchi H. 2004. Isolation of a
new 15-membered macrocyclic glycolipid
lactone, Cuscutic Resinoside a from the
seeds of Cuscuta chinensis: a stimulator of
breast cancer cell proliferation. Planta Med,
70: 299-304.
Van Poppel H, Tombal B. 2011.
Chemoprevention of prostate cancer with
nutrients and supplements. Cancer manag
Res, 3: 91-100.
Yen F-L, Wu T-H, Lin L-T, Lin C-C. 2007.
Hepatoprotective and antioxidant effects of
Cuscuta chinensis against acetaminopheninduced hepatotoxicity in rats. J
Karimi Derman et al.
AJP, Vol. 11, No. 3, May-Jun 2021 268
Ethnopharmacol, 111: 123-128.
Yao CH, Tsai HM, Chen YS, Liu BS. 2005.
Fabrication and evaluation of a new
composite composed of tricalcium
phosphate, gelatin, and Chinese medicine as
a bone substitute. J Biomed Mater Res B, 75:
277-288.
Yu J, Zhou X, He X, Dai M, Zhang Q. 2011.
Curcumin induces apoptosis involving
bax/bcl-2 in human hepatoma SMMC-7721
cells. Asian Pac J Cancer Prev, 12: 1925-
1929.
Zheng H, Dong Z, She J. 1998. Modern study
of traditional Chinese medicine. Xue Yuan
Press, Beijing, China, 3: 2057.
Zeraati F, Zamani A, Goodarzi MT, Hashjin
SMM, Razzaghi K. 2015. In vitro cytotoxic
effects of Cuscuta chinensis whole extract
on human acute lymphoblastic leuke