Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B

Abstract

Bee venom (BV) has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of BV on the colon cancer and their action mechanisms have not been reported yet. We used cell viability assay and soft agar colony formation assay for testing cell viability, electro mobility shift assay for detecting DNA binding activity of nuclear factor kappa B (NF-κB) and Western blotting assay for detection of apoptosis regulatory proteins. We found that BV inhibited growth of colon cancer cells through induction of apoptosis. We also found that the expression of death receptor (DR) 4, DR5, p53, p21, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was increased by BV treatment in a dose dependent manner (0–5 μg/ml). Consistent with cancer cell growth inhibition, the DNA binding activity of nuclear factor kappa B (NF-κB) was also inhibited by BV treatment. Besides, we found that BV blocked NF-κB activation by directly binding to NF-κB p50 subunit. Moreover, combination treatment with BV and p50 siRNA or NF-κB inhibitor augmented BV-induced cell growth inhibition. However, p50 mutant plasmid (C62S) transfection partially abolished BV-induced cell growth inhibiton. In addition, BV significantly suppressed tumor growth in vivo. Therefore, these results suggested that BV could inhibit colon cancer cell growth, and these anti-proliferative effects may be related to the induction of apoptosis by activation of DR4 and DR5 and inhibition of NF-κB.

Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

“…Further, BV administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death [42]. Similar effects on BV were observed in colon cancer cells where activation of death receptors and inhibition of nuclear factor kappa B were observed to be regulating the cancer death [51]. The study demonstrated that BV inhibited growth of colon cancer cells through induction of apoptosis without any effect on FHC colon epithelial normal cells.…”

“…Further, the DNA binding activity of nuclear factor kappa B (NF-κB) was also inhibited by BV treatment. In addition, BV significantly suppressed tumor growth in vivo [51]. …”

Cellular toxicity and biological activities of honey bee (Apis mellifera L.) venom

“…TUNEL ( Figure 1C) and DNA laddering ( Figure 1D) assays results showed that BV induced DNA fragmentation in cells, so it is indeed, the antiproliferative activity of BV involves induction of apoptosis. Although the apoptotic potential of BV has been previously documented (27), the effect on the near normal cells was unclear. Overall, our results suggest that BV displays its pharmacological effects via induction of apoptotic pathway rather than necrosis.…”

Mechanistic and Therapeutic Advances in Colon Cancer: A Systematic Review

“…Bee venom (BV) has anticancer activity and is a traditional medicine for treating skin diseases, cancerous tumors and rheumatism. Recently, Zhenget al have evidence that BV can induce apoptosis by activating DR4 and DR5 and inhibiting NF-kB, thereby inhibiting the growth of colon cancer cells [124].…”

“…People with colon cancer are the result of many factors interacting with obesity, sedentary, diet, alcohol, smoking, low-fi ber intake, high-fat diet, sleep, and lack of exercise are all related to the incidence of colon cancer [133][134][135][136]. Colon cancer can be prevented to a large extent.…”