Is Low-Dose Tamoxifen Useful for the Treatment and Prevention of Breast Cancer?

Wu, Kendall; Brown, Powel H.

doi:10.1093/jnci/95.11.766

Cited by 11 publications

(1 citation statement)

References 16 publications

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“…Although tamoxifen appeared to be more potent than desmethyl-lasiodiplodin in the suppression of breast cancer cell proliferation as well as in the inhibition of MCP-3 survival factor, the favourable therapeutic response to tamoxifen is often associated with severe toxicity such as thromboembolic events and endometrial cancers [41]. Tamoxifen is known to exert a cytotoxic effect, characterized by a strong inhibition of cell proliferation associated with induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis induced by desmethyl-lasiodiplodin is associated with upregulation of apoptotic genes and downregulation of monocyte chemotactic protein-3

Hazalin

Lim²,

Cole

et al. 2013

Anti-Cancer Drugs

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There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%