Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde

Abstract

Cinnamomum verum has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

“…In the same cancer line, similar anticancer effects (inhibition of proliferation and apoptosis induction) were shown after cuminaldehyde treatment [23]. Using hepatocellular carcinoma Hep 3B cells, Perng et al described proapoptotic and anti-inflammatory activities of 2-methoxycinnamaldehyde by inducing the mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and DNA content increase in sub G1 phase and downregulation of NF-κB, cyclooxygenase-2 and prostaglandin E2 levels in vitro and in vivo [24]. In addition, anti-inflammatory effects of EOC were observed in a human skin disease model [25].…”

Curry versus cancer: Potential of some selected culinary spices against cancer with in vitro, in vivo, and human trials evidences

“…Colon cancer (COLO-205) growth was inhibited by cinnamon through its bioactive compound 2-methoxy cinnamaldehyde (2-MCA), administered at 10/20 mg −1 kg −1 , intratumorally to the selected Balb/c mice (Tsai et al, 2016). Growth of SK-Hep-I cells were suppressed by suggesting programed cell death by the administration of 2-MCA to Balb/c nude mice, at a dose of 10 mg kg −1 day −1 (Perng et al, 2016).…”

“…Colon cancer (COLO‐205) growth was inhibited by cinnamon through its bioactive compound 2‐methoxy cinnamaldehyde (2‐MCA), administered at 10/20 mg −1 kg −1 , intratumorally to the selected Balb/c mice (Tsai et al., 2016). Growth of SK‐Hep‐I cells were suppressed by suggesting programed cell death by the administration of 2‐MCA to Balb/c nude mice, at a dose of 10 mg kg −1 day −1 (Perng et al., 2016). The oral administration of cinnamon water extract (CWE) to Balb/c male mice at doses of 20 and 100 mg/kg effectively reduced the serum levels of TNF‐α and IL‐6 (Hong et al., 2012).…”

Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-induced arthritic BALB/c mice

“…There has been a wide array of research into Cinnamomum sp. and their potential roles in cancer (Perng et al 2016), diabetes (Jawale et al 2016), Alzheimer's disease (Madhavadas and Subramanian 2016), end stage renal disease (Mishra et al 2010) and broadly in many oxidative stress mediated diseases like Rheumatoid Arthritis (Hasani-Ranjbar et al 2009;Vetal et al 2013). Literature is, however, lacking in the functional role of CV in RA and the cellular mechanisms by which compounds in the volatile oils of Cinnamomum verum can contribute to the modulation of the immune environment in RA.…”