Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Antheraea proylei J. Sericin Induces Apoptosis in a Caspase-dependent Manner in A549 and HeLa Cells

Author(s): Potsangbam Jolly Devi, Asem Robinson Singh, Naorem Tarundas Singh, Laishram Rupachandra Singh, Sanjenbam Kunjeshwori Devi and Lisam Shanjukumar Singh*

Volume 24, Issue 9, 2024

Published on: 12 February, 2024

Page: [709 - 717] Pages: 9

DOI: 10.2174/1871520623666230329123437

Price: $65

Open Access Journals Promotions 2
Abstract

Background: In spite of much progress in cancer, the global cancer burden is still significant and increasing. Sericin, an adhesive protein of silk cocoons, has been shown to be a potential protein in various biomedical applications, including cancer therapeutics. The present study evaluates the anticancer property of sericin from cocoons of Antheraea proylei J (SAP) against human lung cancer (A549) and cervical cancer (HeLa) cell lines. This is the first report of anti-cancer activity of the non-mulberry silkworm A. proylei J.

Objective: Establish the antiproliferative potential of SAP. 2. Identify the molecular mechanism of cell death induced by SAP on two different cell lines.

Aims: To investigate the anticancer activity of sericin preparation from cocoons of A. proylei.

Methods: SAP was prepared from cocoons of A. proylei J. by the process of the degumming method. Cytotoxic activity was assessed by MTT assay, and genotoxicity was assessed by comet assay. Cleavage of caspase and PARP proteins and phosphorylation of MAPK pathway members were analysed by Western blotting. Cell cycle analysis was done by flow cytometer.

Results: SAP causes cytotoxicity to A549 and HeLa cell lines with the IC50 values 3.8 and 3.9 μg/μl respectively. SAP induces apoptosis in a dose-dependent manner through caspase-3 and p38, MAPK pathways in A549 and HeLa cells. Moreover, in A549 and HeLa cells, SAP induces cell cycle arrest at the S phase in a dose-dependent manner.

Conclusion: The difference in the molecular mechanisms of apoptosis induced by SAP in A549 and HeLa cell lines may be due to the difference in the genotypes of the cancer cell lines. However, further investigation is warranted. The overall results of the present study envisage the possibility of using SAP as an anti-tumorigenic agent.

Keywords: Sericin, Antheraea proylei J., silk cocoons, Caspase-3, PARP, MAPK.

Graphical Abstract
[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Weiderpass, E. Lifestyle and cancer risk. J. Prev. Med. Public Health, 2010, 43(6), 459-471.
[http://dx.doi.org/10.3961/jpmph.2010.43.6.459] [PMID: 21139406]
[3]
Katzke, V.A.; Kaaks, R.; Kühn, T. Lifestyle and cancer risk. Cancer J., 2015, 21(2), 104-110.
[http://dx.doi.org/10.1097/PPO.0000000000000101] [PMID: 25815850]
[4]
Zhang, D.; Wan, L.; Zhang, J.; Liu, C.; Sun, H. Effect of BMAP-28 on human thyroid cancer TT cells is mediated by inducing apoptosis. Oncol. Lett., 2015, 10(4), 2620-2626.
[http://dx.doi.org/10.3892/ol.2015.3612] [PMID: 26622900]
[5]
Gajski, G.; Garaj-Vrhovac, V. Melittin: A lytic peptide with anticancer properties. Environ. Toxicol. Pharmacol., 2013, 36(2), 697-705.
[http://dx.doi.org/10.1016/j.etap.2013.06.009] [PMID: 23892471]
[6]
Hanaoka, Y.; Yamaguchi, Y.; Yamamoto, H.; Ishii, M.; Nagase, T.; Kurihara, H.; Akishita, M.; Ouchi, Y. In vitro and in vivo anticancer activity of human β-defensin-3 and its mouse homolog. Anticancer Res., 2016, 36(11), 5999-6004.
[http://dx.doi.org/10.21873/anticanres.11188] [PMID: 27793926]
[7]
Kundu, S.C.; Dash, B.C.; Dash, R.; Kaplan, D.L. Natural protective glue protein, sericin bioengineered by silkworms: Potential for biomedical and biotechnological applications. Prog. Polym. Sci., 2008, 33(10), 998-1012.
[http://dx.doi.org/10.1016/j.progpolymsci.2008.08.002]
[8]
Kunz, R.I.; Brancalhão, R.M.C.; Ribeiro, L.F.C.; Natali, M.R.M. Silkworm sericin: Properties and biomedical applications. Bio.Med. Res. Int., 2016, 2016, 8175701.
[http://dx.doi.org/10.1155/2016/8175701] [PMID: 27965981]
[9]
Sasaki, M.; Kato, N.; Watanabe, H.; Yamada, H. Silk protein, sericin, suppresses colon carcinogenesis induced by 1,2-dimethylhydrazine in mice. Oncol. Rep., 2000, 7(5), 1049-1052.
[http://dx.doi.org/10.3892/or.7.5.1049] [PMID: 10948337]
[10]
Zhaorigetu, S.; Sasaki, M.; Kato, N. Consumption of sericin suppresses colon oxidative stress and aberrant crypt foci in 1,2-dimethylhydrazine-treated rats by colon undigested sericin. J. Nutr. Sci. Vitaminol., 2007, 53(3), 297-300.
[http://dx.doi.org/10.3177/jnsv.53.297] [PMID: 17874837]
[11]
Zhaorigetu, S.; Sasaki, M.; Watanabe, H.; Kato, N. Supplemental silk protein, sericin, suppresses colon tumorigenesis in 1,2-dimethylhydrazine-treated mice by reducing oxidative stress and cell proliferation. Biosci. Biotechnol. Biochem., 2001, 65(10), 2181-2186.
[http://dx.doi.org/10.1271/bbb.65.2181] [PMID: 11758907]
[12]
Takechi, T.; Wada, R.; Fukuda, T.; Harada, K.; Takamura, H. Antioxidant activities of two sericin proteins extracted from cocoon of silkworm (Bombyx mori) measured by DPPH, chemiluminescence, ORAC and ESR methods. Biomed. Rep., 2014, 2(3), 364-369.
[http://dx.doi.org/10.3892/br.2014.244] [PMID: 24748975]
[13]
Zhaorigetu, S.; Yanaka, N.; Sasaki, M.; Watanabe, H.; Kato, N. Silk protein, sericin, suppresses DMBA-TPA-induced mouse skin tumorigenesis by reducing oxidative stress, inflammatory responses and endogenous tumor promoter TNF-alpha. Oncol. Rep., 2003, 10(3), 537-543.
[PMID: 12684620]
[14]
Kaewkorn, W.; Limpeanchob, N.; Tiyaboonchai, W.; Pongcharoen, S.; Sutheerawattananonda, M. Effects of silk sericin on the proliferation and apoptosis of colon cancer cells. Biol. Res., 2012, 45(1), 45-50.
[http://dx.doi.org/10.4067/S0716-97602012000100006] [PMID: 22688983]
[15]
Kumar, J.P.; Mandal, B.B. Silk sericin induced pro-oxidative stress leads to apoptosis in human cancer cells. Food Chem. Toxicol., 2019, 123, 275-287.
[http://dx.doi.org/10.1016/j.fct.2018.10.063] [PMID: 30391273]
[16]
Zhang, W.M.; Lai, Z.S.; He, M.R.; Xu, G.; Huang, W.; Zhou, D.Y. Effects of the antibacterial peptide cecropins from Chinese oak silkworm, Antheraea pernyi on 1, 2-dimethylhydrazine-induced colon carcinogenesis in rats. Di 1 jun yi da xue xue bao, 2003, 23(10), 1066-1068.
[PMID: 14559696]
[17]
Niu, L.; Yang, S.; Zhao, X.; Liu, X.; Si, L.; Wei, M.; Liu, L.; Cheng, L.; Qiao, Y.; Chen, Z. Sericin inhibits MDA-MB-468 cell proliferation via the PI3K/Akt pathway in triple-negative breast cancer. Mol. Med. Rep., 2021, 23(2), 1-1.
[PMID: 33313947]
[18]
Silva, S.S.; Kundu, B.; Lu, S.; Reis, R.L.; Kundu, S.C. Chinese oak tasar silkworm Antheraea pernyi silk proteins: Current strategies and future perspectives for biomedical applications. Macromol. Biosci., 2019, 19(3), 1800252.
[http://dx.doi.org/10.1002/mabi.201800252] [PMID: 30294916]
[19]
Crowley, L.C.; Christensen, M.E.; Waterhouse, N.J.J.C.S.H.P. Measuring survival of adherent cells with the colony-forming assay. Cold Spring Harb. Protoc., 2016, 2016(8), pdb. prot087171.
[http://dx.doi.org/10.1101/pdb.prot087171]
[20]
Olive, P.L.; Banáth, J.P. The comet assay: A method to measure DNA damage in individual cells. Nat. Protoc., 2006, 1(1), 23-29.
[http://dx.doi.org/10.1038/nprot.2006.5] [PMID: 17406208]
[21]
Häcker, G. The morphology of apoptosis. Cell Tissue Res., 2000, 301(1), 5-17.
[http://dx.doi.org/10.1007/s004410000193] [PMID: 10928277]
[22]
Karanam, G.; Arumugam, M.K. Reactive oxygen species generation and mitochondrial dysfunction for the initiation of apoptotic cell death in human hepatocellular carcinoma HepG2 cells by a cyclic dipeptide Cyclo(-Pro-Tyr). Mol. Biol. Rep., 2020, 47(5), 3347-3359.
[http://dx.doi.org/10.1007/s11033-020-05407-5] [PMID: 32248385]
[23]
Sawant, V.J.; Bamane, S.R.; Kanase, D.G.; Patil, S.B.; Ghosh, J. Encapsulation of curcumin over carbon dot coated TiO2 nanoparticles for pH sensitive enhancement of anticancer and anti-psoriatic potential. RSC Advances, 2016, 6(71), 66745-66755.
[http://dx.doi.org/10.1039/C6RA13851A]
[24]
Mota, N.S.; Kviecinski, M.R.; Felipe, K.B.; GRINEVIcIUS, V.M.; Siminski, T.; Almeida, G.M.; Zeferino, R.C.; Pich, C.T.; Pedrosa, R.C.J.I.J.o.F.N. β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: Study in silico, in vitro and in vivo. Int. J. Funct. Nutr., 2020, 1(1), 1-1.
[http://dx.doi.org/10.3892/ijfn.2020.1]
[25]
Santos, D.C.; Rafique, J.; Saba, S.; Almeida, G.M.; Siminski, T.; Pádua, C.; Filho, D.W.; Zamoner, A.; Braga, A.L.; Pedrosa, R.C.; Ourique, F. Apoptosis oxidative damage‐mediated and antiproliferative effect of selenylated imidazo[1,2‐ a]pyridines on hepatocellular carcinoma HepG2 cells and in vivo. J. Biochem. Mol. Toxicol., 2021, 35(3), e22663.
[http://dx.doi.org/10.1002/jbt.22663] [PMID: 33125183]
[26]
Majtnerová, P.; Roušar, T. An overview of apoptosis assays detecting DNA fragmentation. Mol. Biol. Rep., 2018, 45(5), 1469-1478.
[http://dx.doi.org/10.1007/s11033-018-4258-9] [PMID: 30022463]
[27]
Boulares, A.H.; Yakovlev, A.G.; Ivanova, V.; Stoica, B.A.; Wang, G.; Iyer, S.; Smulson, M. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J. Biol. Chem., 1999, 274(33), 22932-22940.
[http://dx.doi.org/10.1074/jbc.274.33.22932] [PMID: 10438458]
[28]
Yue, J.; López, J.M. Understanding MAPK signaling pathways in apoptosis. Int. J. Mol. Sci., 2020, 21(7), 2346.
[http://dx.doi.org/10.3390/ijms21072346] [PMID: 32231094]
[29]
Park, W.H. MAPK inhibitors, particularly the JNK inhibitor, increase cell death effects in H2O2-treated lung cancer cells via increased superoxide anion and glutathione depletion. Oncol. Rep., 2018, 39(2), 860-870.
[PMID: 29207156]
[30]
Meurer, S.K.; Weiskirchen, R. Usage of Mitogen-activated protein kinase small molecule inhibitors: More than just inhibition. Front. Pharmacol., 2018, 9, 98.
[http://dx.doi.org/10.3389/fphar.2018.00098] [PMID: 29483873]
[31]
Taylor, C.A.; Zheng, Q.; Liu, Z.; Thompson, J.E. Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells. Mol. Cancer, 2013, 12(1), 35.
[http://dx.doi.org/10.1186/1476-4598-12-35] [PMID: 23638878]
[32]
Zhang, L.; Yang, X.; Li, X.; Li, C.; Zhao, L.; Zhou, Y.; Hou, H. Butein sensitizes HeLa cells to cisplatin through the AKT and ERK/p38 MAPK pathways by targeting FoxO3a. Int. J. Mol. Med., 2015, 36(4), 957-966.
[http://dx.doi.org/10.3892/ijmm.2015.2324] [PMID: 26310353]
[33]
Mebratu, Y.; Tesfaigzi, Y. How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle, 2009, 8(8), 1168-1175.
[http://dx.doi.org/10.4161/cc.8.8.8147] [PMID: 19282669]
[34]
Tang, D.; Wu, D.; Hirao, A.; Lahti, J.M.; Liu, L.; Mazza, B.; Kidd, V.J.; Mak, T.W.; Ingram, A.J. ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53. J. Biol. Chem., 2002, 277(15), 12710-12717.
[http://dx.doi.org/10.1074/jbc.M111598200] [PMID: 11821415]
[35]
Cagnol, S.; Chambard, J.C. ERK and cell death: Mechanisms of ERK-induced cell death - apoptosis, autophagy and senescence. FEBS J., 2010, 277(1), 2-21.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07366.x] [PMID: 19843174]
[36]
Wang, X.; Martindale, J.L.; Holbrook, N.J. Requirement for ERK activation in cisplatin-induced apoptosis. J. Biol. Chem., 2000, 275(50), 39435-39443.
[http://dx.doi.org/10.1074/jbc.M004583200] [PMID: 10993883]
[37]
Ambrosino, C.; Nebreda, A.R. Cell cycle regulation by p38 MAP kinases. Biol. Cell, 2001, 93(1-2), 47-51.
[http://dx.doi.org/10.1016/S0248-4900(01)01124-8] [PMID: 11730321]
[38]
Sun, Y.; Tang, S.; Jin, X.; Zhang, C.; Zhao, W.; Xiao, X. Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells. J. Appl. Toxicol., 2013, 33(12), 1500-1505.
[http://dx.doi.org/10.1002/jat.2829] [PMID: 23112108]
[39]
Zhang, Z.; He, H.; Chen, F.; Huang, C.; Shi, X. MAPKs mediate S phase arrest induced by vanadate through a p53-dependent pathway in mouse epidermal C141 cells. Chem. Res. Toxicol., 2002, 15(7), 950-956.
[http://dx.doi.org/10.1021/tx0255018] [PMID: 12119006]
[40]
Wakeman, T.P.; Wyczechowska, D.; Xu, B. Involvement of the p38 MAP kinase in Cr(VI)-induced growth arrest and apoptosis. Mol. Cell. Biochem., 2005, 279(1-2), 69-73.
[http://dx.doi.org/10.1007/s11010-005-8216-1] [PMID: 16283515]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy