To supply reference for further antitumor mechanism studies, the antitumor effect of acylated blueberry anthocyanin (ABA) was studied on H22 murine-transplanted tumor experiment. Mice treated with ABA in combination with cyclophosphamide (CTX) had 53.74% life extension rate. CTX also has significant antineoplastic effect, which could inhibit tumor growth by 63.12%. The spleen and thymus indices decreased by CTX also ameliorated considerably. The activities of alanine aminotransferase and aspartate aminotransferase were significantly lower compared with model group. Malondialdehyde, the product of lipid peroxidation was also decreased. Meanwhile, the activities of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase, were enhanced in a dose-dependent manner (P < .05). Electron microscopy images showed that tumor cells in the mix group had a large sheet of necrosis than the other groups. ABA had strong antitumor effect on H22, as well as synergetic and attenuated toxic effect when combined with CTX.
Cardiac glycosides could increase intracellular Ca 2+ ion by inhibiting the Na + /K + ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae . The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H 22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H 22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.
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