Enhanced anti-metastatic and anti-tumorigenic efficacy of Berbamine loaded lipid nanoparticles in vivo

Abstract

Research on metastasis is gaining momentum for effective cancer management. Berbamine (BBM) has the potency to act as a therapeutic in multiple cancers and cancer metastasis. However, the major limitation of the compound includes poor bioavailability at the tumor site due to short plasma half-life. Here, our major objective involved development of lipid based nanoparticles (NPs) loaded with BBM with an aim to circumvent the above problem. Moreover its, therapeutic potentiality was evaluated through various in vitro cellular studies and in vivo melanoma primary and experimental lung metastatic tumor model in C57BL/6 mice. Results of different cellular experiments demonstrated enhanced therapeutic efficacy of BBM-NPs in inhibiting metastasis, cell proliferation and growth as compared to native BBM in highly metastatic cancer cell lines. Further, in vivo results demonstrated suppression of primary B16F10 melanoma tumor growth in C57BL/6 mice model treated with BBM-NPs than that of native BBM. Importantly, a moderately cytotoxic dose of BBM-NPs was able to significantly suppress the incidence of B16F10 cells lung metastasis in vivo. Results indicated development of an effective approach for aggressive metastatic cancer.

AQP4 Aggregation State Is a Determinant for Glioma Cell Fate

“…To clarify whether the increased capability of AQP4-tetramertransfected glioma cells was related to a different metalloproteinase activity, zymography experiments were performed to analyze the metalloproteinase-9 (MMP9) activity during the invasion process (36,37). The results ( Fig.…”

Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

“…By analysing U-87 glioblastoma cell proliferation at a dosing interval of 48 h, it was observed that berbamine inhibited the growth of cancer cells in a dose-dependent manner with an IC 50 value of 9.8 ± 0.6 µM [7]. Berbamine-treated lung carcinoma cells A549 showed a dose-dependent decrease of viability after 48 h of treatment, with an estimated IC 50 value of 34.63 ± 1.12 µM [15]. Another recent study by Zhang et al described the suppression of proliferation of colorectal cancer cells HCT116 and SW480 by a 48 h treatment with berbamine.…”

“…Zhang and coworkers observed the apoptosis-inducing effect of berbamine in colorectal cancer cells by activating p53-dependent apoptotic signalling pathways [14]. Additionally, another recent study showed enhanced antimetastatic and antitumorigenic efficacy of berbamineloaded lipid nanoparticles in vivo [15]. In the study of Jia et al, berbamine and paclitaxel were tested for their synergistic antitumor effects via the reactive oxygen species ROS/Akt pathway in glioma cells; berbamine has been shown to be a promising adjuvant to conventional chemotherapy of malignant glioma [7].…”

The Multi-Functional Calcium/Calmodulin Stimulated Protein Kinase (CaMK) Family: Emerging Targets for Anti-Cancer Therapeutic Intervention

“…The main limitation for the use of berbamine clinically as an anti-cancer agent is its short plasma half-life and poor bioavailability at the tumour site after systemic administration. To circumvent this, lipid-based nanoparticles loaded with berbamine have been developed and have been shown to decrease primary tumour growth in a B16F10 mouse melanoma model and also suppress the incidence of lung metastases in vivo [181]. This highlights that newer mechanisms of drug delivery may be useful clinically to increase the cancer-specificity of these drugs, without enhancing toxicity.…”