Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice

• Published in: Experimental Oncology
• Date: 2012
• Main Authors: Bozeman, E.N., Srivatsan, S., Mohammadi, H., Daniels, D., Shashidharamurthy, R., Selvaraj, P.
• Format: Article
• Language: English
• Published: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2012
• Subjects: Original contributions
• Online Access: https://nasplib.isofts.kiev.ua/handle/123456789/139880
• Journal Title: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Cite this: Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice / E.N. Bozeman, S. Srivatsan, H. Mohammadi, D. Daniels, R. Shashidharamurthy, P. Selvaraj // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 340-347. — Бібліогр.: 40 назв. — англ.

Despite the recent advances in anti-cancer therapies, breast cancer accounts for the highest percentage of estimated new cases among female cancer patients. The anti-cancer drug Ukrain, a plant-derived semi-synthetic compound, has been shown to be effective in a variety of tumor models including colon, brain, ovarian, melanoma and lymphoma. However, the direct cytotoxic effects of Ukrain have yet to be investigated in breast cancer models. Aim: Herein, we investigated the in vitro and in vivo cytotoxicity of Ukrain using murine (4T07 and TUBO) and human (SKBR-3) breast cancer cell lines. Methods: Cells were treated with varying concentrations of Ukrain for up to 72 h and analyzed for viability by trypan blue exclusion, apoptosis by intracellular caspase 3 and Annexin V staining, and proliferative potential by a clonogenic assay. Female BALB/c mice were challenged subcutaneously (s.c.) with 4T07-RG cells and administered 5 mg/kg or 12.5 mg/kg body weight Ukrain intravenously (i.v.) on the same day and 3 days later. Protective immune responses were determined following re-challenge of tumor-free mice 35 days post primary challenge. Results: Ukrain exposure induced apoptosis in a dose and time-dependent manner with 50 µg/mL Ukrain leading to >50% cell death after 48 h exposure for all three breast cancer cell lines. Ukrain administration (12.5 mg/kg) led to significant inhibition of 4T07 tumor growth in vivo and sustained protective anti-tumor immunity following secondary challenge. Conclusion: Our findings demonstrate the in vitro and in vivo cytotoxic effects of Ukrain on breast cancer cells and may provide insight into designing Ukrain-based therapies for breast cancer patients.