KEY FINDINGS: T. corymbosa (Roxb. ex Wall.) parts are used as poultice, boiled juice, decoctions and infusions for treatment against ulceration, fracture, post-natal recovery, syphilis, fever, tumours and orchitis in Malaysia, China, Thailand and Bangladesh. Studies recorded alkaloids as the predominant phytochemicals in addition to phenols, saponins and sterols with vast bioactivities such as antimicrobial, analgesic, anthelmintic, vasorelaxation, antiviral and cytotoxicity.
SUMMARY: An evaluation of scientific data and traditional medicine revealed the medicinal uses of different parts of T. corymbosa (Roxb. ex Wall.) across Asia. Future studies exploring the structure-bioactivity relationship of alkaloids such as jerantinine and vincamajicine among others could potentially improve the future application towards reversing anticancer drug resistance.
Purpose: In this study, we have investigated the cytotoxic effects of the B. javanica hexane, ethanolic extracts against colon cancer cells. HT29 colon cells were selected as an in vitro cancer model to evaluate the anticancer activity of B. javanica ethanolic extract (BJEE) and the possible mechanisms of action that induced apoptosis.
Methods: 3-(4,5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were performed to determine the antiproliferative and apoptosis validation of BJEE on cancer cells. Measurement of reactive oxygen species (ROS) production, caspase activities, nucleus factor-κB activity, and gene expression experiments was done to investigate the potential mechanisms of action in the apoptotic process.
Results: The results obtained from this study illustrated the significant antiproliferative effect of BJEE on colorectal cancer cells, with a concentration value that inhibits 50% of the cell growth of 25±3.1 µg/mL after 72 h of treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer cells, and BJEE induced cell apoptosis via activation of caspase-8 along with modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor-related apoptosis-inducing ligands, and tumor necrosis factor receptors, which confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS production in treated cells subsequently activated caspase-9 production, which triggered the intrinsic pathways. In addition, overexpression of cytochrome-c, Bax, and Bad proteins along with suppression of Bcl-2 illustrated that mitochondrial-dependent pathway also contributed to BJEE-induced cell death. Consistent with the findings from this study, BJEE-induced cancer cell death proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent events.
Conclusion: From the evidence obtained from this study, it is concluded that the BJEE is a promising natural extract to combat colorectal cancer cells (HT29 cells) via induction of apoptosis through activation of extrinsic and intrinsic pathways.
AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.
MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).
RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.
CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.