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Molecular mechanism of C-phycocyanin induced apoptosis in LNCaP cells.
Bioorg Med Chem 2020; 28(3):115272BM

Abstract

The usefulness of Marine-derived products as the source of anticancer agents has been explored for many decades. The objective of our study was to investigate the molecular mechanism by which C-PC induces apoptosis in monotherapy as well as in combination treatment with a known chemotherapeutic drug named Topotecan (TPT) using prostate cancer cells (LNCaP). To determine the intracellular mechanism of action, we analyzed the gene expression profile of C-PC treated cells using human apoptosis RT2 profiler PCR array, which indicated that C-PC was able to regulate both anti- and pro-apoptotic genes significantly. Detailed analysis revealed increases in the levels of Bax, Apaf-1 (pro-apoptotic proteins) along with the activation of the key apoptotic proteases such as caspase-8, caspase-9, and caspase-3. Similarly, analysis of anti-apoptotic proteins demonstrated a decrease in the expression of Bcl-2, Mcl-1, and survivin. Results from the whole-cell incubation studies indicated that C-PC was only binding to the plasma membrane-associated receptor proteins. LNCaP cells treated with C-PC alone and in combination with TPT showed increased expression of the death receptor FAS (also known as FAS or CD95) along with cleaved PARP, confirming its importance. Our study is significant since it is providing greater insight into the apoptotic mechanisms triggered by C-PC as well as emphasizing the involvement of FAS in mediating its effects. Furthermore, our results with combination treatments suggest that-PC could improve the anticancer effects of drugs such as TPT that are currently used for cancer treatments. In addition, use of C-PC in combination can also diminish the side effects resulting from conventional chemotherapeutic agents such as TPT.

Authors+Show Affiliations

Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, USA.Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, USA.Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, USA.Department of Biological Sciences, Florida International University, Miami, FL, USA.Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL, USA; College of Pharmacy, Health Professions Division, Nova Southeastern University, Fort Lauderdale, FL, USA. Electronic address: appu@nova.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31883786

Citation

Kaur, Paramjot, et al. "Molecular Mechanism of C-phycocyanin Induced Apoptosis in LNCaP Cells." Bioorganic & Medicinal Chemistry, vol. 28, no. 3, 2020, p. 115272.
Kaur P, Dhandayuthapani S, Venkatesan T, et al. Molecular mechanism of C-phycocyanin induced apoptosis in LNCaP cells. Bioorg Med Chem. 2020;28(3):115272.
Kaur, P., Dhandayuthapani, S., Venkatesan, T., Gantor, M., & Rathinavelu, A. (2020). Molecular mechanism of C-phycocyanin induced apoptosis in LNCaP cells. Bioorganic & Medicinal Chemistry, 28(3), p. 115272. doi:10.1016/j.bmc.2019.115272.
Kaur P, et al. Molecular Mechanism of C-phycocyanin Induced Apoptosis in LNCaP Cells. Bioorg Med Chem. 2020 Feb 1;28(3):115272. PubMed PMID: 31883786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mechanism of C-phycocyanin induced apoptosis in LNCaP cells. AU - Kaur,Paramjot, AU - Dhandayuthapani,Sivanesan, AU - Venkatesan,Thiagarajan, AU - Gantor,Miroslav, AU - Rathinavelu,Appu, Y1 - 2019/12/18/ PY - 2019/06/07/received PY - 2019/12/03/revised PY - 2019/12/13/accepted PY - 2019/12/31/pubmed PY - 2019/12/31/medline PY - 2019/12/30/entrez KW - Apaf-1/caspases KW - Bax/Bcl-2 KW - C-PC uptake KW - Cell membrane receptors KW - DNA fragmentation KW - Extrinsic and intrinsic apoptosis signals KW - Limnothrix KW - Mcl-1/survivin KW - PARP cleavage KW - Topotecan SP - 115272 EP - 115272 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 28 IS - 3 N2 - The usefulness of Marine-derived products as the source of anticancer agents has been explored for many decades. The objective of our study was to investigate the molecular mechanism by which C-PC induces apoptosis in monotherapy as well as in combination treatment with a known chemotherapeutic drug named Topotecan (TPT) using prostate cancer cells (LNCaP). To determine the intracellular mechanism of action, we analyzed the gene expression profile of C-PC treated cells using human apoptosis RT2 profiler PCR array, which indicated that C-PC was able to regulate both anti- and pro-apoptotic genes significantly. Detailed analysis revealed increases in the levels of Bax, Apaf-1 (pro-apoptotic proteins) along with the activation of the key apoptotic proteases such as caspase-8, caspase-9, and caspase-3. Similarly, analysis of anti-apoptotic proteins demonstrated a decrease in the expression of Bcl-2, Mcl-1, and survivin. Results from the whole-cell incubation studies indicated that C-PC was only binding to the plasma membrane-associated receptor proteins. LNCaP cells treated with C-PC alone and in combination with TPT showed increased expression of the death receptor FAS (also known as FAS or CD95) along with cleaved PARP, confirming its importance. Our study is significant since it is providing greater insight into the apoptotic mechanisms triggered by C-PC as well as emphasizing the involvement of FAS in mediating its effects. Furthermore, our results with combination treatments suggest that-PC could improve the anticancer effects of drugs such as TPT that are currently used for cancer treatments. In addition, use of C-PC in combination can also diminish the side effects resulting from conventional chemotherapeutic agents such as TPT. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/31883786/Molecular_mechanism_of_C-phycocyanin_induced_apoptosis_in_LNCaP_cells L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(19)30949-6 DB - PRIME DP - Unbound Medicine ER -