The Extract ofHibiscus syriacusInducing Apoptosis by Activating p53 and AIF in Human Lung Cancer Cells

Abstract

Natural products including plants, microorganisms and marine life provide rich resources for anticancer drug discovery. The root bark of Hibiscus syriacus has been used as an antipyretic, anthelmintic and antifungal agent in Asia. The antiproliferative effects of H. syriacus on human lung cancer cells were evaluated with bio-assays. The apoptotic activity was detected by Hoechst 33342 DNA staining and annexin V staining. The expression of caspases, p53, apoptosis induced factor (AIF), Bcl-2 and Bax were evaluated with Western blotting. The in vivo anticancer activity was evaluated using A549-xenograft model. The acetone extract of H. syriacus (HS-AE) exhibited a better cytotoxic effect on lung cancer cells than its methanol extract (HS-ME) or water extract (HS-WE). The IC(50) values of HS-AE on A549 (adenocarcinoma), H209 (squamous cell carcinoma) or H661 (large cell carcinoma) lung cancer cells ranged from 14 to 22 microg/ml after 48 hours of treatment. After 48 hours of exposure, HS-AE (15 microg/ml) induced A549 cell apoptosis to 48 +/- 3.6% of the control. Using Western blotting, HS-AE appears to suppress the expression of p53 and AIF. The results of the in vivo study showed that HS-AE suppresses growth in A549 subcutaneous xenograft tumors. These results indicate that HS-AE exerts significant and dose-dependent antiproliferative effects on cancer cells in vitro and in vivo, which prompts us to further evaluate and elucidate the bioactive component(s) of H. syriacus.

Pharmacological evidences for the extracts and secondary metabolites from plants of the genus Hibiscus

“…The molecules with the coumarin core inhibited monoamine oxidase in vitro in a dosedependent manner, while the coumarin derivative and clemicosin were potent antioxidative agents in vitro (Yun et al, 1999 More recently, the antiproliferative effect of an acetone extract of the root bark of H. syriacus was reported on human lung cancer cells in culture and using in vivo models, employing A549-xenograft. In this study, it was shown that this extract suppressed the expression of the proto-oncogene p53 and the apoptosis initiation factor (AIF), which can explain the cytotoxic effect of this extract, although the exact mechanisms and the molecules involved remain unclear (Cheng, Lee, Harn, Huang, & Chang, 2008).…”

Petroleum ether extract of Chenopodium album L. prevents cell growth and induces apoptosis of human lung cancer cells

“…Chinese medicinal herbs have been widely been used as a folk medicine for centuries in China and southeast Asia (16–18). However, empirical studies related to the action mechanisms of the phytochemicals from these widely used Chinese medicinal herbs remain insufficient.…”

“…To date, various anti-cancer drugs targeting cancer cell apoptosis have been developed from natural chemicals (23,16). The present study demonstrated that the PE extract of C. album L. affected the cellular morphology of human non-small cell lung cancer A549 cells, and their proliferative abilities.…”

Activation of p53/miR‐34a Tumor Suppressor Axis by Chinese Herbal Formula JP‐1 in A549 Lung Adenocarcinoma Cells

“…A variety of small molecule or peptidic compounds had been developed to inhibit MDM2 [7]. On the other hand, many herbal extracts have been shown to induce growth arrest or apoptosis of cancer cells via p53 activation [8–13]. Thus, the Chinese herbal medicine represents a potential resource for searching for proper agent to restore p53 function of cancer cells.…”