Enhancement of cytotoxicity and induction of apoptosis by cationic nano-liposome formulation of n-butylidenephthalide in breast cancer cells

Abstract

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.

Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications

“…DTPLNs showed time-and pHdependent drug release, which led to enhanced antitumor effectiveness of MTO and DOX compared to their free forms in MCF-7 and PC-3 tumor cells. Furthermore, Huang et al [165] found that n-butylidenephthalide (BP) suppressed the proliferation of SK-BR-3 colon cancer cells, and BP/LPPC (Lipo-PEG-PEI Complex) increased its cytotoxicity by stabilizing the BP activity in CT-26 colon carcinoma and RAW 264.7 macrophage. By accelerating the efficiency of entrapment to cause cell death and cell cycle arrest, LPPC encapsulation effectively increased BP cytotoxicity.…”

Mitochondria-Targeted Lipid Nanoparticles Loaded with Rotenone as a New Approach for the Treatment of Oncological Diseases

“…Interestingly, based on the diffusion release exponent values (n), the mechanisms of the ROT release from the PC/Chol/IA-n(OH) and PC/Chol/TPPB-n liposomes were different. The PC/Chol/IA-n(OH) liposomes were characterized by Fickian diffusion (n ˂ 0.45), while for the PC/Chol/TPPB-n liposomes, the The main challenge in the field of cancer treatment is the insufficient selectivity of the systems toward tumor cells [82,83]. Therefore, the next step of the biological activity study was focused on evaluating the cytotoxicity of the ROT-loaded liposomes toward the tumor and normal cell lines in vitro.…”