Background
The natural compound
n
-butylidenephthalide (BP) can pass through the blood–brain barrier to inhibit the growth of glioblastoma multiforme tumors. However, BP has an unstable structure that reduces its antitumor activity and half-life in vivo.
Objective
The aim of this study is to design a drug delivery system to encapsulate BP to enhance its efficacy by improving its protection and delivery.
Methods
To protect its structural stability against protein-rich and peroxide solutions, BP was encapsulated into a lipo-PEG-PEI complex (LPPC). Then, the cytotoxicity of BP/LPPC following preincubation in protein-rich, acid/alkaline, and peroxide solutions was analyzed by MTT. Cell uptake of BP/LPPC was also measured by confocal microscopy. The therapeutic effects of BP/LPPC were analyzed in xenograft mice following intratumoral and intravenous injections.
Results
When BP was encapsulated in LPPC, its cytotoxicity was maintained following preincubation in protein-rich, acid/alkaline, and peroxide solutions. The cytotoxic activity of encapsulated BP was higher than that of free BP (~4.5- to 8.5-fold). This increased cytotoxic activity of BP/LPPC is attributable to its rapid transport across the cell membrane. In an animal study, a subcutaneously xenografted glioblastoma multiforme mouse that was treated with BP by intratumoral and intravenous administration showed inhibited tumor growth. The same dose of BP/LPPC was significantly more effective in terms of tumor inhibition.
Conclusion
LPPC encapsulation technology is able to protect BP’s structural stability and enhance its antitumor effects, thus providing a better tool for use in cancer therapy.
Melanoma, which has a high metastatic capacity and death rate, is a common skin cancer in Western countries. The purpose of this study was to address whether Juniperus communis (JCo) extract is effective in the suppression of melanoma and to elucidate the anticancer mechanisms involved in vitro and in vivo. The antitumor capacities of JCo extract on tumor suppression and toxicity were evaluated and the results demonstrated that the tumor burden was reduced via mediation of cell cycle, reduction of autocrine signaling, and induction of apoptosis. Moreover, JCo extract significantly prolonged the survival rate of the test subjects with only low pathological and physiological toxicity. Additionally, JCo extract also reduced cancer stem cell-related angiogenic and metastatic proteins in the process of tumor elimination. Based on these results, this study suggests that JCo extract suppresses tumor growth and induces apoptosis, and JCo extract may be useful for the prevention of melanoma tumorigenesis.
Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.
Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.
Glioblastoma (GBM) is a common and
aggressive brain tumor with
a median survival of 12–15 months. Temozolomide (TMZ) is a
first-line chemotherapeutic agent used in GBM therapy, but the occurrence
of drug resistance limits its antitumor activity. The natural compound
cedrol has remarkable antitumor activity and is derived from Cedrus atlantica. In this study, we investigated the combined
effect of TMZ and cedrol in GBM cells in vitro and in vivo. The TMZ
and cedrol combination treatment resulted in consistently higher suppression
of cell proliferation via regulation of the AKT and MAPK signaling
pathways in GBM cells. The combination treatment induced cell cycle
arrest, cell apoptosis, and DNA damage better than either drug alone.
Furthermore, cedrol reduced the expression of proteins associated
with drug resistance, including O
6-methlyguanine-DNA-methyltransferase
(MGMT), multidrug resistance protein 1 (MDR1), and CD133 in TMZ-treated
GBM cells. In the animal study, the combination treatment significantly
suppressed tumor growth through the induction of cell apoptosis and
decreased TMZ drug resistance. Moreover, cedrol-treated mice exhibited
no significant differences in body weight and improved TMZ-induced
liver damage. These results imply that cedrol may be a potential novel
agent for combination treatment with TMZ for GBM therapy that deserves
further investigation.
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