Abstract
Heptaphylline derivatives are carbazoles in Clausena harmandiana, a medicinal plant that is utilized for headache, stomach ache, and other treatments of illness. The present study examined the effects of heptaphylline and 7-methoxyheptaphylline on apoptosis of human colon adenocarcinoma cells (HT-29 cell line). Quantification of cell viability was performed using cell proliferation assay (MTT assay) and of protein expression through immunoblotting. The results showed that only heptaphylline, but not 7-methoxyheptaphylline, significantly significantly activated cleaved of caspase-3 and poly (ADP-ribose) polymerase (PARP-1) which resulted in HT-29 cell death. We found that heptaphylline activated BH3 interacting-domain death agonist (Bid) and Bak, proapoptotic proteins. In contrast, it suppressed X-linked inhibitor-of-apoptosis protein (XIAP), Bcl-xL and survivin, inhibitors of apoptosis. In addition, heptaphylline inhibited activation of NF-κB/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and IKKα, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells .
Highlights
Cancer is a disease of deregulated cell proliferation and inhibition of apoptosis
To understand the mechanism by which heptaphylline exerts its apoptotic effects, we examined the effect of heptaphylline on the expression of key proteins involved in apoptosis regulation including BH3 interacting-domain death agonist (Bid), Bak, Bcl-2, Bcl-xL, Mcl-1, X-linked inhibitor-of-apoptosis protein (XIAP), and survivin by using immunoblotting assay
Heptaphylline and 7-methoxyheptaphylline are a carbarzole isolated from the roots of Clausena harmandiana which exhibited cytotoxicity against NCI-H187 and KB cells (Ito et al, 2000; Yenjai et al, 2000; Thongthoom et al, 2011; Wangboonskul and Yenjai., 2012)
Summary
Cancer is a disease of deregulated cell proliferation and inhibition of apoptosis. The treatment of cancers has broadly been unsuccessful because of its uncontrolled growth It is highly required for the improvement of novel and effective chemotherapeutic agents, which contains a capacity to target various signaling pathways to interfere cell growth signaling, to promote the death of cancer cells. It had been found that carbazole alkaloids showed various pharmacological properties, consisting of anticancer, antiplatelet aggregation and vasorelaxing, antimycobacterial, anti HIV-1, antiplasmodial, antimycobial, anti-inflamatory, and cytotoxicity against the leukemia cell line , through inhibiting topoisomerase II and antidiabetes activity (Ito et al, 2000, Yenjai et al, 2000; Songsiang et al, 2011). The major carbazole components in C. harmandiana were heptaphylline and 7-methoxyheptaphylline (Figure 1A), which showed cytotoxicity against the NCI-H187 cell line (Thongthoom et al, 2001). This study investigates the apoptotic effects of heptaphylline and 7-methoxyheptaphylline from C. harmandiana on HT29 colorectal adenocarcinoma cells
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