Tuftsin Augments Antitumor Efficacy of Liposomized Etoposide against Fibrosarcoma in Swiss Albino Mice

Abstract

Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer. Incorporating such drugs into liposomes not only reduces toxicity but also enhances the therapeutic index. Some antioxidants and potent immunomodulators have also been shown to impart significant antitumor activity presumably by nonspecific activation of the host immune system. In the present study, we evaluated augmentation of the antitumor activity of etoposide (ETP) by the immunomodulator tuftsin in Swiss albino mice with fibrosarcoma. The efficacies of the free form of ETP, liposomized ETP (Lip-ETP), and tuftsin-bearing liposomized ETP (Tuft-Lip-ETP) formulations were evaluated on the basis of tumor regression, effect on expression level of p53wt and p53mut, and survival of the treated animals. Tuft-Lip-ETP, when administered at a dosage of 10 mg/kg body weight/day for five days, significantly reduced tumor volume, delayed tumor growth, and also up-regulated the expression of p53wt. In contrast, although Lip-ETP delayed tumor growth, it did not decrease tumor size. The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes is a promising treatment strategy for various forms of cancers, including fibrosarcoma.

Resveratrol suppresses human cervical carcinoma cell proliferation and elevates apoptosis via the mitochondrial and p53 signaling pathways

“…The NC membranes were incubated with the primary antibodies for 2 h at room temperature or overnight at 4°C. Subsequently, the membranes were washed with PBS and incubated with the secondary antibody for 2 h at 4°C ( 16 ). Next, HRP substrate (dilution, 1:1,000) was added and the NC membranes were imaged (Kodak, Japan).…”

<p>Nanomedicine-based formulations containing &omega;-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases</p>

“…44 It is worth highlighting that tuftsin was also previously administered in combination with antineoplastic drugs and shown to enhance their antitumor activity. 46,47 The treatment with tuftsin-tagged liposomes containing the ω-3 PUFA conjugate 41 increased the survival of the hepatocarcinomabearing mice, and this effect was partly related to the markedly reduced expression of COX-2 and Bcl-2, as well as the upregulation of Bax observed in hepatocellular carcinomas. In our opinion, the co-presence of tuftsin and ω-3 PUFAs inside the same nanoliposomes is significant, since ω-3 PUFAs also show both immunomodulatory and antineoplastic activities…”

Immunotherapy for Bone and Soft Tissue Sarcomas

“…It has been demonstrated that tuftsin improves the efficacy of antibiotics against protozoan, bacterial, and fungal infections. Besides, tuftsin-bearing liposomized etoposide enhanced the therapeutic efficacy in murine fibrosarcoma models [ 128 ].…”