Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry


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

Research Article

Transcriptionomic Study on Apoptosis of SKOV-3 Cells Induced by Phycoerythrin from Gracilaria lemaneiformis

Author(s): Jun Ying, Zhouhao Tang, Guanan Zhao, Xia Li, Ruowang Pan, Shuangxiang Lin, Yang Lou, Wanping Wang, Peizhen Li*, Qiyu Bao* and Chunxia Yan*

Volume 21, Issue 10, 2021

Published on: 08 September, 2020

Page: [1240 - 1249] Pages: 10

DOI: 10.2174/1871520620666200908102621

Price: $65


Objective: To investigate the effects of Phycoerythrin (PE) on the human ovarian cancer cell line SKOV-3 and its antitumor mechanisms from a transcriptional point of view.

Methods: SKOV-3 cells were exposed to different concentrations of phycoerythrin. The efficiency of this treatment was evaluated through cell growth inhibition, changes in cell morphology, apoptosis and intracellular ROS levels. High throughput sequencing (RNA-seq) was performed to screen Differentially Expressed Genes (DEGs), which was verified using RT-PCR and Western blotting.

Results: PE showed a significant inhibitory effect on the growth of SKOV-3 cells in a time- and dose-dependent manner. H&E staining, electron microscopy and flow cytometry revealed that PE induced apoptosis in SKOV-3 cells. Transcriptome analysis showed that 2963 genes were differentially expressed between untreated or PEtreated cells. GO and KEGG pathway analyses identified 16 classical pathways that were enriched. We verified 8 DEGs including, JNK, GADD45A, EDEM2, RAD23, UBQLN, CAPN1, XBP1, and OS9. These results were consistent with the results from transcriptional sequences.

Conclusion: The inhibitory effect of PE on SKOV-3 cells was a result of interaction with multiple pathways and signaling molecules. Among these, the ROS/JNK/Bcl-2 signaling pathway, upregulation of JNK, GADD45A and RAD23 as well as downregulation of XBP1 and OS9 played a critical role in the PE -induced apoptosis in human ovarian cancer cells.

Keywords: Phycoerythrin, SKOV-3 cell, RNA-Seq, apoptosis, molecular mechanisms, Gracilaria lemaneiformis.

Graphical Abstract
Gu, D.; Lazo-Portugal, R.; Fang, C.; Wang, Z.; Ma, Y.; Knight, M.; Ito, Y. Purification of R-phycoerythrin from Gracilaria lemaneiformis by centrifugal precipitation chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1087-1088, 138-141.
[] [PMID: 29738963]
Madamwar, D.; Patel, D.K.; Desai, S.N.; Upadhyay, K.K.; Devkar, R.V. Apoptotic potential of C-phycoerythrin from Phormidium sp. A27DM and Halomicronema sp. A32DM on human lung carcinoma cells. EXCLI J., 2015, 14, 527-539.
[PMID: 26535041]
Leney, A.C.; Tschanz, A.; Heck, A.J.R. Connecting color with assembly in the fluorescent B-phycoerythrin protein complex. FEBS J., 2018, 285(1), 178-187.
[] [PMID: 29148254]
Pan, Q.; Chen, M.; Li, J.; Wu, Y.; Zhen, C.; Liang, B. Antitumor function and mechanism of phycoerythrin from Porphyra haitanensis. Biol. Res., 2013, 46(1), 87-95.
[] [PMID: 23760420]
Chen, M.Z.; Ge, A.S.; Cui, P.J.; Liao, Z.H. Study on inhibition effects of Phycoerythrin from Gracilaria lemaneiformis on Hela cells and its mechanism. Shipin Kexue, 2007, 28, 549-552.
Senthilkumar, N.; Kurinjimalar, C.; Thangam, R.; Suresh, V.; Kavitha, G.; Gunasekaran, P.; Rengasamy, R. Further studies and biological activities of macromolecular protein R-Phycoerythrin from Portieria hornemannii. Int. J. Biol. Macromol., 2013, 62, 107-116.
[] [PMID: 23962717]
Tan, H.; Gao, S.; Zhuang, Y.; Dong, Y.; Guan, W.; Zhang, K.; Xu, J.; Cui, J. R-phycoerythrin induces SGC-7901 apoptosis by arresting cell cycle at S phase. Mar. Drugs, 2016, 14(9), 166.
[] [PMID: 27626431]
Qi, H.; Liu, Y.; Qi, X.; Liang, H.; Chen, H.; Jiang, P.; Wang, D. Dietary recombinant phycoerythrin modulates the gut microbiota of H22 tumor-bearing mice. Mar. Drugs, 2019, 17(12), 665.
[] [PMID: 31779128]
Ying, J.; Ren, P.; Shao, H.G.; Li, X.; Ying, J.L.; Zhang, H.Q.; Yao, W.; Pan, R.W.; Li, P.Z. Isolation of PE subunits from Gracilaria lemaneiformis and its inhibitory effect on SW-480 cell line. Zhongguo Weishengtaixue Zazhi, 2012, 24, 298-301.
Ma, S.; Bao, J.Y.J.; Kwan, P.S.; Chan, Y.P.; Tong, C.M.; Fu, L.; Zhang, N.; Tong, A.H.Y.; Qin, Y.R.; Tsao, S.W.; Chan, K.W.; Lok, S.; Guan, X.Y. Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma. Gastroenterology, 2012, 143(3), 675-686.
[] [PMID: 22705009]
Ouyang, Y.; Pan, J.; Tai, Q.; Ju, J.; Wang, H. Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq. Tumour Biol., 2016, 37(8), 10827-10838.
[] [PMID: 26880586]
Li, P.; Ying, J.; Chang, Q.; Zhu, W.; Yang, G.; Xu, T.; Yi, H.; Pan, R.; Zhang, E.; Zeng, X.; Yan, C.; Bao, Q.; Li, S. Effects of phycoerythrin from Gracilaria lemaneiformis in proliferation and apoptosis of SW480 cells. Oncol. Rep., 2016, 36(6), 3536-3544.
[] [PMID: 27748904]
Wang, Z.; Zhou, Z.G.; Wang, C.; Zheng, X.L.; Wang, R.; Li, F.Y.; Guo, J.; Jiang, L.L. Regional micrometastasis of low rectal cancer in mesorectum: A study utilizing HE stain on whole-mount section and ISH analyses on tissue microarray. Cancer Invest., 2006, 24(4), 374-381.
[] [PMID: 16777689]
Pan, R.; Lu, R.; Zhang, Y.; Zhu, M.; Zhu, W.; Yang, R.; Zhang, E.; Ying, J.; Xu, T.; Yi, H.; Li, J.; Shi, M.; Zhou, L.; Xu, Z.; Li, P.; Bao, Q. Spirulina phycocyanin induces differential protein expression and apoptosis in SKOV-3 cells. Int. J. Biol. Macromol., 2015, 81, 951-959.
[] [PMID: 26410814]
Ying, J.; Wang, J.; Ji, H.; Lin, C.; Pan, R.; Zhou, L.; Song, Y.; Zhang, E.; Ren, P.; Chen, J.; Liu, Q.; Xu, T.; Yi, H.; Li, J.; Bao, Q.; Hu, Y.; Li, P. Transcriptome analysis of phycocyanin inhibitory effects on SKOV-3 cell proliferation. Gene, 2016, 585(1), 58-64.
[] [PMID: 26995654]
Patel, S.N.; Sonani, R.R.; Jakharia, K.; Bhastana, B.; Patel, H.M.; Chaubey, M.G.; Singh, N.K.; Madamwar, D. Antioxidant activity and associated structural attributes of Halomicronema phycoerythrin. Int. J. Biol. Macromol., 2018, 111, 359-369.
[] [PMID: 29307804]
Vazquez, A.; Bond, E.E.; Levine, A.J.; Bond, G.L. The genetics of the p53 pathway, apoptosis and cancer therapy. Nat. Rev. Drug Discov., 2008, 7(12), 979-987.
[] [PMID: 19043449]
Bogoyevitch, M.A.; Kobe, B. Uses for JNK: The many and varied substrates of the c-Jun N-terminal kinases. Microbiol. Mol. Biol. Rev., 2006, 70(4), 1061-1095.
[] [PMID: 17158707]
Park, M.H.; Kim, J.H.; Chung, Y.H.; Lee, S.H. Bakuchiol sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins. Biochem. Biophys. Res. Commun., 2016, 473(2), 586-592.
[] [PMID: 27033605]
Zhang, L.; Yang, Z.; Liu, Y. GADD45 proteins: Roles in cellular senescence and tumor development. Exp. Biol. Med. (Maywood), 2014, 239(7), 773-778.
[] [PMID: 24872428]
Su, L.Y.; Xin, H.Y.; Liu, Y.L.; Zhang, J.L.; Xin, H.W.; Su, X.L. Anticancer Bioactive Peptide (ACBP) inhibits gastric cancer cells by upregulating growth arrest and DNA damage-inducible gene 45A (GADD45A). Tumour Biol., 2014, 35(10), 10051-10056.
[] [PMID: 25015188]
Bullard, S.A.; Seo, S.; Schilling, B.; Dyle, M.C.; Dierdorff, J.M.; Ebert, S.M.; DeLau, A.D.; Gibson, B.W.; Adams, C.M. Gadd45a protein promotes skeletal muscle atrophy by forming a complex with the protein kinase MEKK4. J. Biol. Chem., 2016, 291(34), 17496-17509.
[] [PMID: 27358404]
Ji, H.; Huang, C.; Wu, S.; Kasim, V. XBP1-s promotes colorectal cancer cell proliferation by inhibiting TAp73 transcriptional activity. Biochem. Biophys. Res. Commun., 2019, 508(1), 203-209.
[] [PMID: 30473215]
Li, H.; Chen, X.; Gao, Y.; Wu, J.; Zeng, F.; Song, F. XBP1 induces snail expression to promote epithelial- to-mesenchymal transition and invasion of breast cancer cells. Cell. Signal., 2015, 27(1), 82-89.
[] [PMID: 25280941]
Zhang, G.H.; Kai, J.Y.; Chen, M.M.; Ma, Q.; Zhong, A.L.; Xie, S.H.; Zheng, H.; Wang, Y.C.; Tong, Y.; Tian, Y.; Lu, R.Q.; Guo, L. Downregulation of XBP1 decreases serous ovarian cancer cell viability and enhances sensitivity to oxidative stress by increasing intracellular ROS levels. Oncol. Lett., 2019, 18(4), 4194-4202.
[] [PMID: 31579421]
Yu, H.Y.; Ou, Y.S.; Zhong, S.X.; Zuo, Q.; Chen, Y.Y.; Xu, S.; Li, Y.Q. Silencing XBP1 expression enhances the sensitivity of human osteosarcoma HOS cells to MPPα-PDT. Tumor, 2020, 40, 31-40.
Soni, S.; Padwad, Y.S. HIF-1 in cancer therapy: Two decade long story of a transcription factor. Acta Oncol., 2017, 56(4), 503-515.
[] [PMID: 28358664]
Sun, Y.W.; Chen, Y.F.; Li, J.; Huo, Y.M.; Liu, D.J.; Hua, R.; Zhang, J.F.; Liu, W.; Yang, J.Y.; Fu, X.L.; Yan, T.; Hong, J.; Cao, H. A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma. Br. J. Cancer, 2014, 111(11), 2131-2141..
[] [PMID: 25314054]
Wang, F.; Zhu, B.B. Effects of propofol on the proliferation; apoptosis and invasion of SCC-74 cells via HIF-1α signal pathway. Practical Oncol. J., 2020, 34(2), 120-125.

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