Bee venom inhibits growth of human cervical tumors in mice.
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.
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Hye Lim
HL
Lee
Clinical Research Laboratory, Uijeonbu St. Mary's Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Republic of Korea.
Sang Ho
SH
Park
College of Veterinary Medicine, Chungbuk National University, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Tae Myoung
TM
Kim
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Yu Yeon
YY
Jung
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Mi Hee
MH
Park
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Sang Hyun
SH
Oh
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Hye Seok
HS
Yun
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Hyung Ok
HO
Jun
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Hwan Soo
HS
Yoo
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Sang-Bae
SB
Han
Department of Food Science & Technology, Korea National University of Transportation, Jeungpyeong, Republic of Korea.
Ung Soo
US
Lee
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.
Joo Hee
JH
Yoon
Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon, Republic of Korea.
Min Jong
MJ
Song
College of Pharmacy and Medical Research Center, Heungduk, Cheongju, Chungbuk, Republic of Korea.
Jin Tae
JT
Hong
D000818:Animals; D017209:Apoptosis; D001514:Bee Venoms / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000378:metabolism; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays; D019014:fas Receptor / Q000378:metabolism
D001514:Bee Venoms; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C114109:TNFRSF21 protein, human; C506033:TNFRSF25 protein, human; C485251:Tnfrsf21 protein, mouse; C506034:Tnfrsf25 protein, mouse; D019014:fas Receptor
NF-κB; apoptosis; bee venom; cervical cancer; death receptors