AI Article Synopsis
- Elevated methionine (MET) requirement in cancer cells, known as MET dependence, presents a unique metabolic flaw that can be targeted to inhibit cancer growth.
- Recombinant methioninase (rMETase) has shown effectiveness in slowing tumor growth in mouse models, with oral administration (o-rMETase) proving to be more effective than intraperitoneal injection (ip-rMETase) while maintaining low toxicity.
- The combination of o-rMETase with ip-rMETase resulted in complete tumor growth arrest, highlighting its potential for clinical use in cancer therapy and possibly even in promoting healthy aging.
Article Abstract
The elevated methionine (MET) requirement of cancer cells is termed MET dependence and is possibly the only known general metabolic defect in cancer. Targeting MET by recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro and in vivo due to their elevated requirement for MET. rMETase can also potentiate chemotherapy drugs active in S phase due to the selective arrest of cancer cells in S/G phase during MET restriction (MR). We previously reported that rMETase, administrated by intraperitoneal injection (ip-rMETase), could inhibit tumor growth in mouse models of cancer including patient-derived orthotopic xenograft (PDOX) mouse models. We subsequently compared ip-rMETase and oral rMETase (o-rMETase) on a melanoma PDOX mouse model. o-rMETase was significantly more effective than ip-rMETase to inhibit tumor growth without overt toxicity. The combination of o-rMETase+ip-rMETase was significantly more effective than either monotherapy and completely arrested tumor growth. Thus, o-rMETase is effective as an anticancer agent with the potential of clinical development for chronic cancer therapy as well as for cancer prevention. o-rMETase may also have potential as an antiaging agent for healthy people, since MR has been shown to extend the life span of a variety of different organisms.
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| http://dx.doi.org/10.1007/978-1-4939-8796-2_24 | DOI Listing |
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