1.Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression.
Zhao B1, Li X1. Oncol Rep. 2014 Jun;31(6):2769-75. doi: 10.3892/or.2014.3126. Epub 2014 Apr 3.
Human bladder cancer is an aggressive tumor which frequently resists chemotherapy. Therefore, the search for new therapeutic agents is of great importance. Altholactone, isolated from Goniothalamus sp., has been reported to inhibit the growth of various types of cancer cells. However, no prior research has been conducted to demonstrate the antiproliferative potential of altholactone on bladder cancer. In the present study, we characterized the effect of altholactone on cell growth and apoptosis in bladder cancer T24 cells. Treatment with altholactone resulted in a significant reduction in cell viability, induction of apoptosis and generation of reactive oxygen species (ROS) in T24 cells. Furthermore, our results revealed that altholactone-induced apoptosis was associated with decreased expression of Akt phosphorylation and activation of MAPK‑p38. Altholactone treatment was also found to result in a significant loss of mitochondrial membrane potential, Bcl-2 downregulation and caspase-3 activation.
2.Halogenated benzoate derivatives of altholactone with improved anti-fungal activity.
Euanorasetr J1,2, Junhom M2, Tantimavanich S3, Vorasin O4, Munyoo B4, Tuchinda P4, Panbangred W1,2. J Asian Nat Prod Res. 2016 May;18(5):462-74. doi: 10.1080/10286020.2015.1133611. Epub 2016 Jan 14.
Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml(-1) against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1-15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml(-1), while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11-13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml(-1). In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group.
3.Role of altholactone in inducing type II apoptosis signalling pathway and expression of cancer-related genes in cervical carcinoma HeLa cell line.
Uthaisang-Tanechpongtamb W1, Sriyabhaya P, Wilairat P. Cell Biol Int. 2013 May;37(5):471-7. doi: 10.1002/cbin.10059. Epub 2013 Mar 13.
Goniothalamus species (Annonaceae) is a shrub that grows in the rainforest of tropical Asia. Several compounds have been isolated and exhibit the potential use for cancer treatment. In this work, altholactone isolated from Goniothalamus macrophyllus was investigated for its cytotoxicity, apoptosis signalling and the expression of cancer-related genes in the cervical carcinoma HeLa cells. Cytotoxicity was evaluated by MTT assay. Apoptotic characteristics were evaluated by morphological studies. Caspase-3 activity was detected using a fluorogenic substrate. Cytochrome c release from mitochondria and protein Bid were determined by Western blotting and cancer-related genes expression by RT-PCR. The results demonstrated that altholactone was cytotoxic to HeLa (IC50 = 9.6 μg/mL), and apoptotic cell death was manifested by appearance of chromatin condensation and caspase-3 activation, which was inhibited by specific inhibitors of both caspase-8 and -9.
4.(+)-Altholactone exhibits broad spectrum immune modulating activity by inhibiting the activation of pro-inflammatory cytokines in RAW 264.7 cell lines.
Johnson TA1, Sohn J, Ward AE, Cohen TL, Lorig-Roach ND, Chen H, Pilli RA, Widjaja EA, Hanafi M, Kardono LB, Lotulung PD, Boundy-Mills K, Bjeldanes LF. Bioorg Med Chem. 2013 Jul 15;21(14):4358-64. doi: 10.1016/j.bmc.2013.04.055. Epub 2013 Apr 28.
An evaluation of Indonesian plants to identify compounds with immune modulating activity revealed that the methanolic extract of an Alphonsea javanica Scheff specimen possessed selective anti-inflammatory activity in a nuclear factor-kappa B (NF-κB) luciferase and MTT assay using transfected macrophage immune (Raw264.7) cells. A high-throughput LC/MS-ELSD based library approach of the extract in combination with the NF-κB and MTT assays revealed the styryl lactone (+)-altholactone (2) was responsible for the activity. Compound 2, its acetylated derivate (+)-3-O-acetylaltholactone (3), and the major compound of this class, (+)-goniothalmin (1), were further evaluated to determine their anti-inflammatory potential in the NF-κB assay. Concentration-response studies of 1-3 indicated that only 2 possessed NF-κB based anti-inflammatory activity. Compound 2 reduced the LPS-induced NO production, phosphorylation of IκBα, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using Western blot analysis.