Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells

Abstract

• α-Humulene and sclareol showed synergistic inhibitory effect on human pancreatic cancer cells. • The combination strongly decreased the levels of NF-κB, phosphor Akt (pAkt) and Bcl-2, and increased the level of Bax. • The in vivo study showed that HUM and SCL in combination suppressed the growth of Panc-1 xenograft tumors in immunodeficient mice. Both α-Humulene (HUM) and sclareol (SCL) are naturally occurred compounds and have been shown to exert anti-inflammatory and anticancer activities. The effects of these two compounds alone or in combination on pancreatic cancer cells have not been reported. In the present study, we investigated the effects of HUM and SCL on human pancreatic cancer cells cultured in vitro and grown as xenograft tumors in vivo. In the in vitro studies, we found that HUM and SCL in combination synergistically inhibited the growth of pancreatic cancer cells. The combination strongly stimulated apoptosis, and suppressed migration, invasion and sphere formation in pancreatic cells. Studies on the mechanism of action showed that the combination strongly decreased the levels of NF-κB, phosphor Akt (pAkt) and Bcl-2, and increased the level of Bax. Knockdown of NF-κB and Akt by small interfering RNA (siRNA) abrogated the inhibitory effect of HUM and SCL on pancreatic cancer cells. The in vivo study showed that HUM and SCL in combination suppressed the growth of Panc-1 xenograft tumors in immunodeficient mice. Results of the present study indicate that HUM and SCL in combination may represent an effective approach for inhibiting the growth of pancreatic cancer.