Bee venom inhibits growth of human cervical tumors in mice

// Hye Lim Lee 1, * , Sang Ho Park 2, * , Tae Myoung Kim 3 , Yu Yeon Jung 1 , Mi Hee Park 1 , Sang Hyun Oh 1 , Hye Seok Yun 1 , Hyung Ok Jun 1 , Hwan Soo Yoo 1 , Sang-Bae Han 1 , Ung Soo Lee 4 , Joo Hee Yoon 5 , Min Jong Song 6 , Jin Tae Hong 1 1 College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea 2 Clinical Research Laboratory, Uijeonbu St. Mary's Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Republic of Korea 3 College of Veterinary Medicine, Chungbuk National University, Heungduk, Cheongju, Chungbuk, Republic of Korea 4 Department of Food Science & Technology, Korea National University of Transportation, Jeungpyeong, Republic of Korea 5 Department of Obstetrics and Gynecology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Paldal-gu, Suwon, Gyeonggi-do, Republic of Korea 6 Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon, Republic of Korea * These authors have contributed equally to this work Correspondence to: Jin Tae Hong e-mail: jinthong@chungbuk.ac.kr Min Jong Song e-mail: bitsugar@catholic.ac.kr Keywords: bee venom, apoptosis, death receptors, NF-κB, cervical cancer Received: November 27, 2014      Accepted: January 08, 2015      Published: January 23, 2015 ABSTRACT We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1–5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.