Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines

被引:9
|
作者
Dhanya, Dhanyalayam [1 ]
Giuseppe, Palma [2 ]
Rita, Cappello A. [1 ]
Annaluisa, Mariconda [3 ]
Stefaniaa, Sinicropi M. [1 ]
Francesca, Giordano [1 ]
Vitale, Del V. [2 ]
Anna, Ramunno [4 ]
Claudio, Arra [2 ]
Pasquale, Longo [3 ]
Carmela, Saturnino [5 ,6 ]
机构
[1] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, Via Pietro Bucci,Edificio Polifunz, I-87036 Arcavacata Di Rende, CS, Italy
[2] Fdn G Pascale, IRCCS, Ist Nazl Tumori, SSD Sperimentaz Anim, Via M Semmola, I-80131 Naples, NA, Italy
[3] Univ Salerno, Dept Chem & Biol, I-84084 Fisciano, SA, Italy
[4] Univ Salerno, Dept Pharmaceut & Biomed Sci, I-84084 Fisciano, SA, Italy
[5] Univ Basilicata, Dept Sci, I-85100 Potenza, PZ, Italy
[6] Univ Basilicata, I-85100 Potenza, PZ, Italy
关键词
Lipophilic phosphonium salts; Human tumor cell lines; anticancer drugs; reactive oxygen species; mitochondria; cell cycle; SELECTIVE MITOCHONDRIAL ACCUMULATION; ANTICARCINOMA ACTIVITY; BIOLOGICAL EVALUATION; ANTIPROLIFERATIVE ACTIVITY; INDUCED APOPTOSIS; CARCINOMA-CELLS; IN-VITRO; DERIVATIVES; RHODAMINE-123; INHIBITION;
D O I
10.2174/1871520617666170719154249
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aims/Objective: Phosphonium salts are compounds whose structural characteristics enable them to cross the plasma and mitochondrial membrane with ease. Cancer cells have higher plasma membrane potentials than normal cells; phosphonium salts selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function. Method: In the present work, we investigated the cytotoxic activity of lipophilic phosphonium salt (11-methoxy11- oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of the two new phosphine oxide salts, 3,3'-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3' (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa). Result: We showed that only MUTP exhibits antiproliferative effects on both cell lines, without affecting the normal breast epithelial cell proliferation. More specifically, we demonstrated that MUTP treatment of breast cancer cells is associated with impaired cell-cycle progression and metabolically induces mitochondrial damage and triggers apoptotic cell death in MCF-7 and HeLa cells. Taken together, these findings suggest that MUTP may be capable of selectively targeting neoplastic cell growth and therefore has potential applications as anticancer agent.
引用
收藏
页码:1796 / 1804
页数:9
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