Anticancer Potential of Fruit Extracts from Vatica diospyroides Symington Type SS and Their Effect on Program Cell Death of Cervical Cancer Cell Lines.

Vatica diospyroides Symington is locally known as Chan-Ka-Pho in Thailand. Ancient people have used it as therapeutic plant for cardiac and blood tonic cure. The purpose of this study was to investigate the potential cytotoxicity and selectivity of the extracts from V. diospyroides type SS fruit on cervical cancer HeLa and SiHa cell lines and to examine its underlying mechanism of action. MTT assay revealed that the extracts showed inhibition of cell survival in a dose-dependent manner and exhibited highly cytotoxic activity against both HeLa and SiHa cells with IC50 value less than 20 µg/mL along with less toxicity against L929 cells. Acetone cotyledon extract (ACE) showed the best selectivity index value of 4.47 (HeLa) and 3.51 (SiHa). Distinctive morphological changes were observed in ACE-treated cervical cancer cells contributing to apoptosis action. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that ACE induced apoptosis in HeLa and SiHa cell lines in a dose-dependent manner. Treatment of ACE with half IC50 caused DNA fragmentation and also activated increasing of bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The results suggest that ACE has potent and selective cytotoxic effect against cervical cancer cells and the potential to induce bax and caspase-8-dependent apoptosis. Hence, the ACE could be further exploited as a potential lead in cancer treatment.

New neolignans from the seeds of Myristica fragrans and their cytotoxic activities.

Three new dihydrobenzofuran neolignans, myticaganal A-C (1-3), along with five known compounds (4-8), were isolated from the seeds of Myristica fragrans. Their structures were elucidated by extensive spectroscopic analysis. In vitro cytotoxic activities of the isolated compounds against three human cancer cell lines (KB, oral cavity; MCF-7, breast cancer; and NCI-H187, small cell lung cancer) were evaluated. Neolignan 3 showed significant cytotoxicity against KB and NCI-H187 cell lines with IC50 values of 5.9 and 6.3 µM, respectively.

(-)-Kusunokinin and piperloguminine from Piper nigrum: An alternative option to treat breast cancer.

Several studies have reported that active compounds isolated from Piper nigrum possess anticancer properties. However, there are no data on anticancer activity of (-)-kusunokinin and piperlonguminine. The purposes of this study were to isolate active compounds from P. nigrum and identify the molecular mechanisms underlying growth and apoptosis pathway in breast cancer cells. Two bioactive compounds, (-)-kusunokinin and piperlonguminine, were isolated from P. nigrum. Cytotoxicity and the molecular mechanism were measured by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and Western blot analysis. We found that the active compounds, which effect cancer cell lines were (-)-kusunokinin and piperlonguminine. These compounds have potent cytotoxic effects on breast cancer cells (MCF-7 and MDA-MB-468) and colorectal cells (SW-620). (-)-Kusunokinin demonstrated a cytotoxic effect on MCF-7 and MDA-MB-468 with IC50 values of 1.18 and 1.62µg/mL, respectively. Piperlonguminine had a cytotoxic effect on MCF-7 and MDA-MB-468 with IC50 values of 1.63 and 2.19µg/mL, respectively. Both compounds demonstrated lower cytotoxicity against normal breast cell lines with IC50 values higher than 11µg/mL. Cell cycle and apoptotic analysis using flow cytometry, showed that the (-)-kusunokinin and piperlonguminine induced cell undergoing apoptosis and drove cells towards the G2/M phase. Moreover, both compounds decreased topoisomerase II and bcl-2. The increasing of p53 levels further increased p21, bax, cytochrome c, caspase-8, -7 and -3 activities, except caspase-9. These results suggest that the (-)-kusunokinin and piperlonguminine have been shown to have potent anticancer activities through extrinsic pathway and G2/M phase arrest.

Two new antimalarial quassinoid derivatives from the stems of Brucea javanica.

Phytochemical investigation of the stems from Brucea javanica led to the isolation of two new quassinoids, brujavanol C (1) and brujavanol D (2), together with six known compounds (3-8). The chemical structures were elucidated by means of various spectroscopic methods. All the isolated compounds were evaluated for antimalarial activity against Plasmodium falciparum and compounds 6 and 7 exhibited the most potent activity against the K1 strain, with IC50 values of 1.41 and 1.06 µM, respectively.

Extracts from Vatica diospyroides type SS fruit show low dose activity against MDA-MB-468 breast cancer cell-line via apoptotic action.

Very strong antiproliferative action of V. diospyroides type SS fruit extracts (IC50 range of 1.60-17.45 µg/mL) in MDA-MB-468 cell-line was observed in an MTT assay. After dosing of an extract concentration at half IC50 to cell line for 24 to 72 hours, treated cells were subjected to Annexin V-FITC/PI binding assay, followed by FACS and western blot analyses. Significant apoptotic death was observed with all extract treatments and both exposure times. Dosing with acetone extract of pericarp and cotyledon induced the highest apoptotic populations (33 and 32%, resp.), with the lowest populations of viable cells (65 and 67%, resp.). During 24 to 72 hours of dosing with methanolic extract of pericarp, the populations of viable and early apoptotic cells decreased significantly from 72.40 to 71.32% and from 12.00 to 6.36%, respectively, while the late apoptotic and nonviable cell populations continuously increased from 15.30 to 19.18% and from 0.30 to 3.14%, respectively. The expression of Bax increased within 12-48 hours of dosing, confirming apoptosis induced by time-dependent responses. The mutant p53 of MDA-MB-468 cells was expressed. Our results indicate that apoptosis and time-dependent therapeutic actions contribute to the cytotoxic effects of V. diospyroides type SS fruit on MDA-MB-468 cell.

Propagation of Vatica diospyroides symington: an endangered medicinal dipterocarp of peninsular Thailand by cultures of embryonic axes and leaf-derived calli.

Embryonic axes and young leaves of Vatica diospyroides Symington were excised sterilely and then cultured on MS medium supplemented with 0-20 mg L(-1) of a growth regulator and 0-0.3% Activated Charcoal (AC). The growth regulators tested were 2, 4-Dichlorophenoxyacetic acid (2,4-D), alpha-Naphthaleneacetic acid (NAA) and 3, 6-Dichloro-2-methoxybensoic acid (Dicamba). Vigorous shoot development was observed with 0-20 mg L(-1) of each plant growth regulator and 0.1-0.15% AC. Shoot-derived calli were obtained 6 months after culturing embryonic axes on MS medium, with 15 mg L(-1) dicamba and 0.1% AC. Interestingly, after culturing young leaves for 2 months, the highest weight of compact calli (0.40 g) was achieved with a medium containing 20 mg L(-1) dicamba and 0.1% AC, in darkness. These were successfully multiplied by renewing and culturing in the same medium and transfer to shooting induction in MS medium supplemented with 0-20 mg L(-1) 6-benzyladenine (BA). Unfortunately, shoot induction from calli was unsuccessful and despite initiated roots being induced. A successful in vitro propagation protocol of V. diospyroides should be thus investigated more extensively.