Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells.
In the present study, we developed a novel drug-like self-micellizing anticancer lipid (SMAL), and investigated its anticancer activity and effects on cell death pathways in human colorectal cancer (CRC) cell lines. Three self-assembled nanoparticles were prepared, namely, SMAL102 (lauramide derivative), SMAL104 (palmitamide derivative), and SMAL108 (stearamide derivative) by a thin-film hydration technique, and were characterized for physicochemical and biological parameters. SMAL102 were nanosized (160.23 ± 8.11 nm) with uniform spherical shape, while SMAL104 and SMAL108 did not form spherical shape but formed large size nanoparticles and irregular in shape. Importantly, SMAL102 showed a cytotoxic effect towards CRC cell lines (HCT116 and HT-29), and less toxicity to a normal colon fibroblast cell line (CCD-18Co). Conversely, SMAL104 and SMAL108 did not have an anti-proliferative effect on CRC cell lines. SMAL102 nanoparticles were actively taken up by CRC cell lines, localized in the cell membrane, and exhibited remarkable cytotoxicity in a concentration-dependent manner. The normal colon cell line showed significantly less cellular uptake and non-cytotoxicity as compared with the CRC cell lines. SMAL102 nanoparticles induced caspase-3, caspase-9, and PARP cleavage in HT-29 cells, indicating the induction of apoptosis; whereas LC3B was activated in HCT116 cells, indicating autophagy-induced cell death. Collectively, these results demonstrate that SMAL102 induced cell death via activation of apoptosis and autophagy in CRC cell lines. The present study could be a pioneer for further preclinical and clinical development of such compounds.
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea.
Pasupathi
P
Sundaramoorthy
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea.
Rengarajan
R
Baskaran
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea; Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar 470003, India.
Siddhartha Kumar
SK
Mishra
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea.
Keun-Yeong
KY
Jeong
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea.
Seung Hyun
SH
Oh
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea.
Bong
B
Kyu Yoo
Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea. Electronic address: hwanmook@gachon.ac.kr.
Hwan Mook
HM
Kim
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008823:Micelles; D053758:Nanoparticles
D000970:Antineoplastic Agents; D008055:Lipids; D008823:Micelles
Apoptosis; Autophagy; Colorectal cancer; Nanoparticle; Self-micellizing anticancer lipid